BRCA1

Breast cancer 1, early onset

PDB rendering based on 1jm7.
Available structures
PDB Ortholog search: PDBe, RCSB
Identifiers
SymbolsBRCA1 ; BRCAI; BRCC1; BROVCA1; IRIS; PNCA4; PPP1R53; PSCP; RNF53
External IDsOMIM: 113705 MGI: 104537 HomoloGene: 5276 ChEMBL: 5990 GeneCards: BRCA1 Gene
RNA expression pattern
More reference expression data
Orthologs
SpeciesHumanMouse
Entrez67212189
EnsemblENSG00000012048ENSMUSG00000017146
UniProtP38398P48754
RefSeq (mRNA)NM_007294NM_009764
RefSeq (protein)NP_009225NP_033894
Location (UCSC)Chr 17:
41.2 – 41.28 Mb		Chr 11:
101.49 – 101.55 Mb
PubMed search
Location of the BRCA1 gene on chromosome 17.

BRCA1 and BRCA1 (/ˌbrækəˈwʌn/[1]) are a human gene and its protein product, respectively. The official symbol (BRCA1, italic for the gene, nonitalic for the protein) and the official name (breast cancer 1, early onset) are maintained by the HGNC. Orthologs, styled Brca1 and Brca1, are common in other mammal species.[2] BRCA1 is a human tumor suppressor gene[3][4] (to be specific, a caretaker gene), found in all humans; its protein, also called by the synonym breast cancer type 1 susceptibility protein, is responsible for repairing DNA.[5]

BRCA1 and BRCA2 are normally expressed in the cells of breast and other tissue, where they help repair damaged DNA or destroy cells if DNA cannot be repaired. They are involved in the repair of chromosomal damage with an important role in the error-free repair of DNA double-strand breaks.[6][7] If BRCA1 or BRCA2 itself is damaged by a BRCA mutation, damaged DNA is not repaired properly, and this increases the risk for breast cancer.[8][9] Thus, although the terms "breast cancer susceptibility gene" and "breast cancer susceptibility protein" (used frequently both in and outside the medical literature) sound as if they describe an oncogene, BRCA1 and BRCA2 are normal; it is their mutation that is abnormal.

BRCA1 combines with other tumor suppressors, DNA damage sensors, and signal transducers to form a large multi-subunit protein complex known as the BRCA1-associated genome surveillance complex (BASC).[10] The BRCA1 protein associates with RNA polymerase II, and through the C-terminal domain, also interacts with histone deacetylase complexes. Thus, this protein plays a role in transcription, DNA repair of double-strand breaks[9] ubiquitination, transcriptional regulation as well as other functions.[11]

Methods to diagnose the likelihood of getting cancer of a patient with mutations in BRCA1 and BRCA2 were covered by patents owned or controlled by Myriad Genetics.[12][13] Myriad's business model of offering the diagnostic test exclusively led from Myriad being a startup in 1994 to being a publicly traded company with 1200 employees and about $500M in annual revenue in 2012;[14] it also led to controversy over high prices and the inability to get second opinions from other diagnostic labs, which in turn led to the landmark Association for Molecular Pathology v. Myriad Genetics lawsuit.[15]

Discovery

The first evidence for the existence of such a gene was provided by the King laboratory at UC Berkeley in 1990.[16] Four years later, after an international race to find it,[17] the gene was cloned in 1994 by scientists at University of Utah, National Institute of Environmental Health Sciences (NIEHS) and Myriad Genetics.[12][18]

Gene location

The human BRCA1 gene is located on the long (q) arm of chromosome 17 at region 2 band 1, from base pair 41,196,312 to base pair 41,277,500 (Build GRCh37/hg19) (map).[19] BRCA1 orthologs[2] have been identified in most mammals for which complete genome data are available.

Protein structure

The BRCA1 protein contains the following domains:[20]

This protein also contains nuclear localization signal and nuclear export signal motifs.[21]

The human BRCA1 protein consists of four major protein domains; the Znf C3HC4- RING domain, the BRCA1 serine domain and two BRCT domains. These domains encode approximately 27% of BRCA1 protein. There are six known isoforms of P38398 BRCA1, with isoforms 1 and 2 comprising 1863 amino acids each.

text
Domain map of BRCA1; RING, serine containing domain (SCD), and BRCT domains are indicated. Horizontal black lines indicate protein-binding domains for the listed partners. Red circles mark phosphorylation sites.[22]

Zinc ring finger domain

The RING motif, a Zn finger found in eukaryotic peptides, is 40–60 amino acids long and consists of eight conserved metal-binding residues, two quartets of cysteine or histidine residues that coordinate two zinc atoms.[23] This motif contains a short anti-parallel beta-sheet, two zinc-binding loops and a central alpha helix in a small domain. This RING domain interacts with associated proteins including BARD1, which also contains a RING motif, to form a heterodimer. The BRCA1 RING motif is flanked by alpha helices formed by residues 8–22 and 81–96 of the BRCA1 protein. It interacts with a homologous region in BARD1 also consisting of a RING finger flanked by two alpha-helices formed from residues 36–48 and 101–116. These four helices combine to form a heterodimerization interface and stabilise the BRCA1-BARD1 heterodimer complex. Additional stabilisation is achieved by interactions between adjacent residues in the flanking region and hydrophobic interactions. The BARD1/BRCA1 interaction is disrupted by tumorigenic amino acid substitutions in BRCA1, implying that the formation of a stable complex between these proteins may be an essential aspect of BRCA1 tumor suppression.[23]

The ring domain is an important element of ubiquitin E3 ligases, which catalyse protein ubiquitination. Ubiquitin is a small regulatory protein found in all tissues that directs proteins to compartments within the cell. BRCA1 polypeptides, in particular Lys-48-linked polyubiquitin chains, are dispersed throughout within the resting cell nucleus but when DNA replication begins they gather in restrained groups that also contain BRCA2 and BARD1. BARD1 is thought to be involved in the recognition and binding of protein targets for ubiquitination.[24] It attaches to proteins and labels them for destruction. Ubiquitination occurs via the BRCA1 fusion protein and is abolished by zinc chelation.[23] The enzyme activity of the fusion protein is dependent on the proper folding of the ring domain.

Serine cluster domain

BRCA1 serine cluster domain (SCD) spans amino acids 1280–1524. A portion of the domain is located in exons 11–13. High rates of mutation occur in exons 11–13. Reported phosphorylation sites of BRCA1 are concentrated in the SCD where they are phosphorylated by ATM/ATR kinases both in vitro and in vivo. ATM/ATR are kinases activated by DNA damage. Mutation of serine residues may affect localization of BRCA1 to sites of DNA damage and DNA damage response function.[22]

BRCT domains

The dual repeat BRCT domain of the BRCA1 protein is an elongated structure approximately 70 Å long and 30–35 Å wide.[25] The 85–95 amino acid domains in BRCT can be found as single modules or as multiple tandem repeats containing two domains.[26] Both of these possibilities can occur in a single protein in a variety of different conformations.[25] The C-terminal BRCT region of the BRCA1 protein is essential for repair of DNA, transcription regulation and tumor suppressor function.[27] In BRCA1 the dual tandem repeat BRCT domains are arranged in a head-to-tail-fashion in the three-dimensional structure, burying 1600 Å of hydrophobic, solvent-accessible surface area in the interface. These all contribute to the tightly packed knob-in-hole structure that comprises the interface. These homologous domains interact to control cellular responses to DNA damage. It is, therefore, no surprise that a missense mutation at the interface of these two proteins can have devastating consequences on the cell cycle, resulting in protein dysfunction and a greater risk of developing cancer. The linker that joins these two homologs also needs to be considered, since its poorly defined electron density alludes to a possible complex function; the ability to flex.[25]

Function and mechanism

BRCA1 is part of a complex that repairs double-strand breaks in DNA. The strands of the DNA double helix are continuously breaking as they incur damage. Sometimes one strand is broken, and sometimes both strands are broken simultaneously. DNA cross linking agents are an important source of chromosome/DNA damage. Double-strand breaks occur as intermediates after the crosslinks are removed, and indeed, biallelic mutations in BRCA1 have been identified to be responsible for Fanconi Anemia, Complementation Group S,[28] a genetic disease associated with hypersensitivity to DNA crosslinking agents. BRCA1 is part of a protein complex that repairs DNA when both strands are broken. When both strands are broken, it is difficult for the repair mechanism to "know" how to replace the correct DNA sequence, and there are multiple ways to attempt the repair. The double-strand repair mechanism that BRCA1 participates in is homologous recombination, in which the repair proteins utilize homologous intact sequence from a sister chromatid, from a homologous chromosome, or from the same chromosome (depending on cell cycle phase) as a template.[29] This DNA repair takes place with the DNA in the cell nucleus, wrapped around the histone. Several proteins, including BRCA1, arrive at the histone-DNA complex for this repair. Regulatory aspect to BRCA1 nuclear ⁄ non-nuclear distribution was first shown by Dr Rao laboratory in 1997[30]

In the nucleus of many types of normal cells, the BRCA1 protein interacts with RAD51 during repair of DNA double-strand breaks.[31] These breaks can be caused by natural radiation or other exposures, but also occur when chromosomes exchange genetic material (homologous recombination, e.g., "crossing over" during meiosis). The BRCA2 protein, which has a function similar to that of BRCA1, also interacts with the RAD51 protein. By influencing DNA damage repair, these three proteins play a role in maintaining the stability of the human genome.

BRCA1 is also involved in another type of DNA repair, termed mis-match repair. BRCA1 interacts with the DNA mismatch repair protein MSH2.[32] MSH2, MSH6, PARP and some other proteins involved in single-strand repair are reported to be elevated in BRCA1-deficient mammary tumors.[33]

A protein called valosin-containing protein (VCP, also known as p97) plays a role to recruit BRCA1 to the damaged DNA sites. After ionizing radiation, VCP is recruited to DNA lesions and cooperates with the ubiquitin ligase RNF8 to orchestrate assembly of signaling complexes for efficient DSB repair.[34] BRCA1 interacts with VCP.[35] BRCA1 also interacts with c-Myc, and other proteins that are critical to maintain genome stability.[36]

BRCA1 directly binds to DNA, with higher affinity for branched DNA structures. This ability to bind to DNA contributes to its ability to inhibit the nuclease activity of the MRN complex as well as the nuclease activity of Mre11 alone.[37] This may explain a role for BRCA1 to promote lower fidelity DNA repair by non-homologous end joining (NHEJ).[38] BRCA1 also colocalizes with γ-H2AX (histone H2AX phosphorylated on serine-139) in DNA double-strand break repair foci, indicating it may play a role in recruiting repair factors.[11][39]

Formaldehyde and acetaldehyde are common environmental sources of DNA cross links that often require repairs mediated by BRCA1 containing pathways.[40][41]

Transcription

BRCA1 was shown to co-purify with the human RNA Polymerase II holoenzyme in HeLa extracts, implying it is a component of the holoenzyme.[42] Later research, however, contradicted this assumption, instead showing that the predominant complex including BRCA1 in HeLa cells is a 2 megadalton complex containing SWI/SNF.[43] SWI/SNF is a chromatin remodeling complex. Artificial tethering of BRCA1 to chromatin was shown to decondense heterochromatin, though the SWI/SNF interacting domain was not necessary for this role.[39] BRCA1 interacts with the NELF-B (COBRA1) subunit of the NELF complex.[39]

Other roles

Research suggests that both the BRCA1 and BRCA2 proteins regulate the activity of other genes and play a critical role in embryo development. The BRCA1 protein probably interacts with many other proteins, including tumor suppressors and regulators of the cell division cycle.

Mutations and cancer risk

Further information: BRCA mutation

Certain variations of the BRCA1 gene lead to an increased risk for breast cancer as part of a hereditary breast-ovarian cancer syndrome. Researchers have identified hundreds of mutations in the BRCA1 gene, many of which associated with an increased risk of cancer. Women with an abnormal BRCA1 or BRCA2 gene have up to an 80% risk of developing breast cancer by age 90; increased risk of developing ovarian cancer is about 55% for women with BRCA1 mutations and about 25% for women with BRCA2 mutations.[44]

These mutations can be changes in one or a small number of DNA base pairs (the building-blocks of DNA). Those mutations can be identified with PCR and DNA sequencing.

In some cases, large segments of DNA are rearranged. Those large segments, also called large rearrangements, can be a deletion or a duplication of one or several exons in the gene. Classical methods for mutations detection (sequencing) are unable to reveal those mutations.[45] Other methods are proposed: quantitative PCR,[46] Multiplex Ligation-dependent Probe Amplification (MLPA),[47] and Quantitative Multiplex PCR of Shorts Fluorescents Fragments (QMPSF).[48] New methods have been recently proposed: heteroduplex analysis (HDA) by multi-capillary electrophoresis or also dedicated oligonucleotides array based on comparative genomic hybridization (array-CGH).[49]

Some results suggest that hypermethylation of the BRCA1 promoter, which has been reported in some cancers, could be considered as an inactivating mechanism for BRCA1 expression.[50]

A mutated BRCA1 gene usually makes a protein that does not function properly. Researchers believe that the defective BRCA1 protein is unable to help fix DNA damages leading to mutations in other genes. These mutations can accumulate and may allow cells to grow and divide uncontrollably to form a tumor. Thus, BRCA1 inactivating mutations lead to a predisposition for cancer.

BRCA1 mRNA 3' UTR can be bound by an miRNA, Mir-17 microRNA. It has been suggested that variations in this miRNA along with Mir-30 microRNA could confer susceptibility to breast cancer.[51]

In addition to breast cancer, mutations in the BRCA1 gene also increase the risk of ovarian, fallopian tube, and prostate cancers. Moreover, precancerous lesions (dysplasia) within the Fallopian tube have been linked to BRCA1 gene mutations. Pathogenic mutations anywhere in a model pathway containing BRCA1 and BRCA2 greatly increase risks for a subset of leukemias and lymphomas.[9]

Women having inherited a defective BRCA1 or BRCA2 gene have risks for breast and ovarian cancer that are so high and seem so selective that many mutation carriers choose to have prophylactic surgery. There has been much conjecture to explain such apparently striking tissue specificity. Major determinants of where BRCA1/2 hereditary cancers occur are related to tissue specificity of the cancer pathogen, the agent that causes chronic inflammation or the carcinogen. The target tissue may have receptors for the pathogen, become selectively exposed to an inflammatory process or to a carcinogen. An innate genomic deficit in a tumor suppressor gene impairs normal responses and exacerbates the susceptibility to disease in organ targets. This theory also fits data for several tumor suppressors beyond BRCA1 or BRCA2. A major advantage of this model is that it suggests there may be some options in addition to prophylactic surgery.[52]

Germ line mutations and founder effect

All germ-line BRCA1 mutations identified to date have been inherited, suggesting the possibility of a large “founder” effect in which a certain mutation is common to a well-defined population group and can, in theory, be traced back to a common ancestor. Given the complexity of mutation screening for BRCA1, these common mutations may simplify the methods required for mutation screening in certain populations. Analysis of mutations that occur with high frequency also permits the study of their clinical expression.[53] Examples of manifestations of a founder effect are seen among Ashkenazi Jews. Three mutations in BRCA1 have been reported to account for the majority of Ashkenazi Jewish patients with inherited BRCA1-related breast and/or ovarian cancer: 185delAG, 188del11 and 5382insC in the BRCA1 gene.[54][55] In fact, it has been shown that if a Jewish woman does not carry a BRCA1 185delAG, BRCA1 5382insC founder mutation, it is highly unlikely that a different BRCA1 mutation will be found.[56] Additional examples of founder mutations in BRCA1 are given in Table 1 (mainly derived from [53]).

This is an incomplete list that may never be able to satisfy particular standards for completeness. You can help by expanding it with reliably sourced entries.
Population or subgroup BRCA1 mutation(s)[57] Reference(s)
African-Americans 943ins10, M1775R [58]
Afrikaners E881X [59]
Ashkenazi Jewish 185delAG, 188del11, 5382insC [54][55]
Austrians 2795delA, C61G, 5382insC, Q1806stop [60]
Belgians 2804delAA, IVS5+3A>G [61][62]
Dutch Exon 2 deletion, exon 13 deletion, 2804delAA [61][63][64]
Finns 3745delT, IVS11-2A>G [65][66]
French 3600del11, G1710X [67]
French Canadians C4446T [68]
Germans 5382insC, 4184del4 [69][70]
Greeks 5382insC [71]
Hungarians 300T>G, 5382insC, 185delAG [72]
Italians 5083del19 [73]
Japanese L63X, Q934X [74]
Native North Americans 1510insG, 1506A>G [75]
Northern Irish 2800delAA [76]
Norwegians 816delGT, 1135insA, 1675delA, 3347delAG [77][78]
Pakistanis 2080insA, 3889delAG, 4184del4, 4284delAG, IVS14-1A>G [79]
Polish 300T>G, 5382insC, C61G, 4153delA [80][81]
Russians 5382insC, 4153delA [82]
Scottish 2800delAA [76][83]
Spanish R71G [84][85]
Swedish Q563X, 3171ins5, 1201del11, 2594delC [58][86]

Female fertility

As women age, their reproductive performance declines leading to menopause. This decline is tied to a reduction in the number of ovarian follicles. Although about 1 million oocytes are present at birth in the human ovary, only about 500 (about 0.05%) of these ovulate, and the rest are wasted. The decline in ovarian reserve appears to occur at a constantly increasing rate with age,[87] and leads to nearly complete exhaustion of the reserve by about age 52. As ovarian reserve and fertility decline with age, there is also a parallel increase in pregnancy failure and meiotic errors resulting in chromosomally abnormal conceptions.

Women with a germ-line BRCA1 mutation appear to have a diminished oocyte reserve and decreased fertility compared to normally aging women.[88] Furthermore, women with an inherited BRCA1 mutation undergo menopause prematurely.[89] Since BRCA1 is a key DNA repair protein, these findings suggest that naturally occurring DNA damages in oocytes are repaired less efficiently in women with a BRCA1 defect, and that this repair inefficiency leads to early reproductive failure.

As noted above, the BRCA1 protein plays a key role in homologous recombinational repair. This is the only known cellular process that can accurately repair DNA double-strand breaks. DNA double-strand breaks accumulate with age in humans and mice in primordial follicles.[90] Primordial follicles contain oocytes that are at an intermediate (prophase I) stage of meiosis. Meiosis is the general process in eukaryotic organisms by which germ cells are formed, and it is likely an adaptation for removing DNA damages, especially double-strand breaks, from germ line DNA.[91] (Also see article Meiosis). Homologous recombinational repair employing BRCA1 is especially promoted during meiosis. It was found that expression of 4 key genes necessary for homologous recombinational repair of DNA double-strand breaks (BRCA1, MRE11, RAD51 and ATM) decline with age in the oocytes of humans and mice,[90] leading to the hypothesis that DNA double-strand break repair is necessary for the maintenance of oocyte reserve and that a decline in efficiency of repair with age plays a role in ovarian aging.

Cancer chemotherapy

Non-small cell lung cancer (NSCLC) is the leading cause of cancer deaths worldwide. At diagnosis, almost 70% of persons with NSCLC have locally advanced or metastatic disease. Persons with NSCLC are often treated with therapeutic platinum compounds (e.g. cisplatin, carboplatin or oxaliplatin) that cause inter-strand cross-links in DNA. Among individuals with NSCLC, low expression of BRCA1 in the primary tumor correlated with improved survival after platinum-containing chemotherapy.[92][93] This correlation implies that low BRCA1 in the cancer, and the consequent low level of DNA repair, causes vulnerability of the cancer to treatment by the DNA cross-linking agents. High BRCA1 may protect cancer cells by acting in a pathway that removes the damages in DNA introduced by the platinum drugs. Thus the level of BRCA1 expression is a potentially important tool for tailoring chemotherapy in lung cancer management.[92][93]

Level of BRCA1 expression is also relevant to ovarian cancer treatment. Patients having sporadic ovarian cancer who were treated with platinum drugs had longer median survival times if their BRCA1 expression was low compared to patients with higher BRCA1 expression (46 compared to 33 months).[94]

Patents, enforcement, litigation, and controversy

A patent application for the isolated BRCA1 gene and cancer-cancer promoting mutations discussed above, as well as methods to diagnose the likelihood of getting breast cancer, was filed by the University of Utah, National Institute of Environmental Health Sciences (NIEHS) and Myriad Genetics in 1994;[12] over the next year, Myriad, (in collaboration with investigators at Endo Recherche, Inc., HSC Research & Development Limited Partnership, and University of Pennsylvania), isolated and sequenced the BRCA2 gene and identified key mutations, and the first BRCA2 patent was filed in the U.S. by Myriad and other institutions in 1995.[13] Myriad is the exclusive licensee of these patents and has enforced them in the US against clinical diagnostic labs.[15] This business model led from Myriad being a startup in 1994 to being a publicly traded company with 1200 employees and about $500M in annual revenue in 2012;[14] it also led to controversy over high prices and the inability to get second opinions from other diagnostic labs, which in turn led to the landmark Association for Molecular Pathology v. Myriad Genetics lawsuit.[15][95] The patents begin to expire in 2014.

According to an article published in the journal, Genetic Medicine, in 2010, "The patent story outside the United States is more complicated.... For example, patents have been obtained but the patents are being ignored by provincial health systems in Canada. In Australia and the UK, Myriad’s licensee permitted use by health systems, but announced a change of plans in August 2008. ... Only a single mutation has been patented in Myriad’s lone European-wide patent, although some patents remain under review of an opposition proceeding. In effect, the United States is the only jurisdiction where Myriad’s strong patent position has conferred sole-provide status."[96][97] Peter Meldrum, CEO of Myriad Genetics, has acknowledged that Myriad has "other competitive advantages that may make such [patent] enforcement unnecessary" in Europe.[98]

Legal decisions surrounding the BRCA1 and BRCA2 patents will affect the field of genetic testing in general.[99] A June 2013 article, in Association for Molecular Pathology v. Myriad Genetics (No. 12-398), quoted the US Supreme Court's unanimous ruling that, "A naturally occurring DNA segment is a product of nature and not patent eligible merely because it has been isolated," invalidating Myriad's patents on the BRCA1 and BRCA2 genes. However, the Court also held that manipulation of a gene to create something not found in nature could still be eligible for patent protection.[100] The Federal Court of Australia came to the opposite conclusion, upholding the validity of an Australian Myriad Genetics patent over the BRCA1 gene in February 2013.[101] The Federal Court also rejected an appeal in September 2014.[102]

Interactions

BRCA1 has been shown to interact with the following proteins:

See also

References

  1. ↑ Hamel PJ (2007-05-29). "BRCA1 and BRCA2: No Longer the Only Troublesome Genes Out There". HealthCentral. Retrieved 2010-07-02.
  2. ↑ 2.0 2.1 "OrthoMaM phylogenetic marker: BRCA2 coding sequence".
  3. ↑ Duncan JA, Reeves JR, Cooke TG (October 1998). "BRCA1 and BRCA2 proteins: roles in health and disease". Molecular pathology : MP 51 (5): 237–47. doi:10.1136/mp.51.5.237. PMC 395646. PMID 10193517.
  4. ↑ Yoshida K, Miki Y (November 2004). "Role of BRCA1 and BRCA2 as regulators of DNA repair, transcription, and cell cycle in response to DNA damage". Cancer science 95 (11): 866–71. doi:10.1111/j.1349-7006.2004.tb02195.x. PMID 15546503.
  5. ↑ Check W (2006-09-01). "BRCA: What we know now". College of American Pathologists. Retrieved 2010-08-23.
  6. ↑ Friedenson B (August 2007). "The BRCA1/2 pathway prevents hematologic cancers in addition to breast and ovarian cancers". BMC Cancer 7: 152–162. doi:10.1186/1471-2407-7-152. PMC 1959234. PMID 17683622.
  7. ↑ Friedenson B (2008-06-08). "Breast cancer genes protect against some leukemias and lymphomas" (VIDEO). SciVee.
  8. ↑ "Breast and Ovarian Cancer Genetic Screening". Palo Alto Medical Foundation. Archived from the original on 4 October 2008. Retrieved 2008-10-11.
  9. ↑ 9.0 9.1 9.2 Friedenson B (2007). "The BRCA1/2 pathway prevents hematologic cancers in addition to breast and ovarian cancers". BMC Cancer 7: 152. doi:10.1186/1471-2407-7-152. PMC 1959234. PMID 17683622.
  10. ↑ 10.0 10.1 10.2 10.3 10.4 10.5 10.6 Wang Y, Cortez D, Yazdi P, Neff N, Elledge SJ, Qin J (April 2000). "BASC, a super complex of BRCA1-associated proteins involved in the recognition and repair of aberrant DNA structures". Genes Dev. 14 (8): 927–39. PMC 316544. PMID 10783165.
  11. ↑ 11.0 11.1 Starita LM, Parvin JD (2003). "The multiple nuclear functions of BRCA1: transcription, ubiquitination and DNA repair". Current Opinion in Cell Biology 15 (3): 345–350. doi:10.1016/S0955-0674(03)00042-5. PMID 12787778.
  12. ↑ 12.0 12.1 12.2 US patent 5747282, Skolnick HS, Goldgar DE, Miki Y, Swenson J, Kamb A, Harshman KD, Shattuck-Eidens DM, Tavtigian SV, Wiseman RW, Futreal PA, "7Q-linked breast and ovarian cancer susceptibility gene", issued 1998-05-05, assigned to Myriad Genetics, Inc., The United States of America as represented by the Secretary of Health and Human Services, and University of Utah Research Foundation
  13. ↑ 13.0 13.1 US patent 5837492, Tavtigian SV, Kamb A, Simard J, Couch F, Rommens JM, Weber BL, "Chromosome 13-linked breast cancer susceptibility gene", issued 1998-11-17, assigned to Myriad Genetics, Inc., Endo Recherche, Inc., HSC Research & Development Limited Partnership, Trustees of the University of Pennsylvania
  14. ↑ 14.0 14.1 Myriad Investor Page—see "Myriad at a glance" accessed October 2012
  15. ↑ 15.0 15.1 15.2 Schwartz J (2009-05-12). "Cancer Patients Challenge the Patenting of a Gene". Health. New York Times.
  16. ↑ Hall JM, Lee MK, Newman B, Morrow JE, Anderson LA, Huey B et al. (December 1990). "Linkage of early-onset familial breast cancer to chromosome 17q21". Science 250 (4988): 1684–9. doi:10.1126/science.2270482. PMID 2270482.
  17. ↑ High-Impact Science: Tracking down the BRCA genes (Part 1) - Cancer Research UK science blog, 2012
  18. ↑ Miki Y, Swensen J, Shattuck-Eidens D, Futreal PA, Harshman K, Tavtigian S et al. (October 1994). "A strong candidate for the breast and ovarian cancer susceptibility gene BRCA1". Science 266 (5182): 66–71. doi:10.1126/science.7545954. PMID 7545954.
  19. ↑ National Center for Biotechnology Information, U.S. National Library of Medicine EntrezGene reference information for BRCA1 breast cancer 1, early onset (Homo sapiens)
  20. ↑ Paterson JW (February 1998). "BRCA1: a review of structure and putative functions". Dis. Markers 13 (4): 261–74. PMID 9553742.
  21. ↑ Henderson BR (September 2005). "Regulation of BRCA1, BRCA2 and BARD1 intracellular trafficking". BioEssays 27 (9): 884–93. doi:10.1002/bies.20277. PMID 16108063.
  22. ↑ 22.0 22.1 Clark SL, Rodriguez AM, Snyder RR, Hankins GD, Boehning D (April 2012). "Structure-Function Of The Tumor Suppressor BRCA1". Comput Struct Biotechnol J 1 (1): e201204005. doi:10.5936/csbj.201204005. PMC 3380633. PMID 22737296.
  23. ↑ 23.0 23.1 23.2 23.3 Brzovic PS, Rajagopal P, Hoyt DW, King MC, Klevit RE (October 2001). "Structure of a BRCA1-BARD1 heterodimeric RING-RING complex". Nature Structural & Molecular Biology 8 (10): 833–7. doi:10.1038/nsb1001-833. PMID 11573085.
  24. ↑ Baer R (October 2001). "With the ends in sight: images from the BRCA1 tumor suppressor". Nature Structural & Molecular Biology 8 (10): 822–4. doi:10.1038/nsb1001-822. PMID 11573079.
  25. ↑ 25.0 25.1 25.2 Williams RS, Green R, Glover JN (October 2001). "Crystal structure of the BRCT repeat region from the breast cancer-associated protein BRCA1". Nature Structural & Molecular Biology 8 (10): 838–42. doi:10.1038/nsb1001-838. PMID 11573086.
  26. ↑ Huyton T, Bates PA, Zhang X, Sternberg MJ, Freemont PS (August 2000). "The BRCA1 C-terminal domain: structure and function". Mutat. Res. 460 (3–4): 319–32. doi:10.1016/S0921-8777(00)00034-3. PMID 10946236.
  27. ↑ 27.0 27.1 Joo WS, Jeffrey PD, Cantor SB, Finnin MS, Livingston DM, Pavletich NP (March 2002). "Structure of the 53BP1 BRCT region bound to p53 and its comparison to the Brca1 BRCT structure". Genes Dev. 16 (5): 583–93. doi:10.1101/gad.959202. PMC 155350. PMID 11877378.
  28. ↑ Sawyer SL, Tian L, Kahkonen M, Schwartzentruber J, Kircher M, Majewski J, Dyment DA, Innes AM, Boycott KM, Moreau LA, Moilanen JS, Greenberg RA (2014). "Biallelic Mutations in BRCA1 Cause a New Fanconi Anemia Subtype". Cancer Discov 5 (2): 135–42. doi:10.1158/2159-8290.CD-14-1156. PMID 25472942.
  29. ↑ Kimball's Biologh Pages
  30. ↑ 30.0 30.1 Wang H, Shao N, Ding QM, Cui J, Reddy ES, Rao VN (Jul 1997). "BRCA1 proteins are transported to the nucleus in the absence of serum and splice variants BRCA1a, BRCA1b are tyrosine phosphoproteins that associate with E2F, cyclins and cyclin dependent kinases". Oncogene 15 (2): 143–57. doi:10.1038/sj.onc.1201252. PMID 9244350.
  31. ↑ Boulton SJ (November 2006). "Cellular functions of the BRCA tumour-suppressor proteins". Biochem. Soc. Trans. 34 (Pt 5): 633–45. doi:10.1042/BST0340633. PMID 17052168.
  32. ↑ 32.0 32.1 32.2 32.3 32.4 32.5 Wang Q, Zhang H, Guerrette S, Chen J, Mazurek A, Wilson T et al. (August 2001). "Adenosine nucleotide modulates the physical interaction between hMSH2 and BRCA1". Oncogene 20 (34): 4640–9. doi:10.1038/sj.onc.1204625. PMID 11498787.
  33. ↑ Warmoes M, Jaspers JE, Pham TV, Piersma SR, Oudgenoeg G, Massink MP et al. (July 2012). "Proteomics of mouse BRCA1-deficient mammary tumors identifies DNA repair proteins with potential diagnostic and prognostic value in human breast cancer". Mol. Cell Proteomics 11 (7): M111.013334. doi:10.1074/mcp.M111.013334. PMC 3394939. PMID 22366898.
  34. ↑ Meerang M, Ritz D, Paliwal S, Garajova Z, Bosshard M, Mailand N et al. (November 2011). "The ubiquitin-selective segregase VCP/p97 orchestrates the response to DNA double-strand breaks". Nat. Cell Biol. 13 (11): 1376–82. doi:10.1038/ncb2367. PMID 22020440.
  35. ↑ Zhang H, Wang Q, Kajino K, Greene MI (2000). "VCP, a weak ATPase involved in multiple cellular events, interacts physically with BRCA1 in the nucleus of living cells". DNA Cell Biol 19 (5): 253–263. doi:10.1089/10445490050021168. PMID 10855792.
  36. ↑ 36.0 36.1 36.2 Wang Q, Zhang H, Kajino K, Greene MI (October 1998). "BRCA1 binds c-Myc and inhibits its transcriptional and transforming activity in cells". Oncogene 17 (15): 1939–48. doi:10.1038/sj.onc.1202403. PMID 9788437.
  37. ↑ Paull TT, Cortez D, Bowers B, Elledge SJ, Gellert M (2001). "Direct DNA binding by Brca1". Proceedings of the National Academy of Sciences 98 (11): 6086–6091. doi:10.1073/pnas.111125998. PMC 33426. PMID 11353843.
  38. ↑ Durant ST, Nickoloff JA (2005). "Good timing in the cell cycle for precise DNA repair by BRCA1". Cell Cycle 4 (9): 1216–22. doi:10.4161/cc.4.9.2027. PMID 16103751.
  39. ↑ 39.0 39.1 39.2 Ye Q, Hu YF, Zhong H, Nye AC, Belmont AS, Li R (2001). "BRCA1-induced large-scale chromatin unfolding and allele-specific effects of cancer-predisposing mutations". The Journal of Cell Biology 155 (6): 911–922. doi:10.1083/jcb.200108049. PMC 2150890. PMID 11739404.
  40. ↑ Friedenson B (November 2011). "A common environmental carcinogen unduly affects carriers of cancer mutations: carriers of genetic mutations in a specific protective response are more susceptible to an environmental carcinogen". Med. Hypotheses 77 (5): 791–7. doi:10.1016/j.mehy.2011.07.039. PMID 21839586.
  41. ↑ Ridpath JR, Nakamura A, Tano K, Luke AM, Sonoda E, Arakawa H et al. (December 2007). "Cells deficient in the FANC/BRCA pathway are hypersensitive to plasma levels of formaldehyde". Cancer Res. 67 (23): 11117–22. doi:10.1158/0008-5472.CAN-07-3028. PMID 18056434.
  42. ↑ Scully R, Anderson SF, Chao DM, Wei W, Ye L, Young RA et al. (1997). "BRCA1 is a component of the RNA polymerase II holoenzyme". Proceedings of the National Academy of Sciences 94 (11): 5605–10. doi:10.1073/pnas.94.11.5605. PMC 20825. PMID 9159119.
  43. ↑ Bochar DA, Wang L, Beniya H, Kinev A, Xue Y, Lane WS et al. (2000). "BRCA1 Is Associated with a Human SWI/SNF-Related Complex Linking Chromatin Remodeling to Breast Cancer". Cell 102 (2): 257–265. doi:10.1016/S0092-8674(00)00030-1. PMID 10943845.
  44. ↑ "Genetics". Breastcancer.org. 2012-09-17.
  45. ↑ Mazoyer S (May 2005). "Genomic rearrangements in the BRCA1 and BRCA2 genes". Hum. Mutat. 25 (5): 415–22. doi:10.1002/humu.20169. PMID 15832305.
  46. ↑ Barrois M, Bièche I, Mazoyer S, Champème MH, Bressac-de Paillerets B, Lidereau R (February 2004). "Real-time PCR-based gene dosage assay for detecting BRCA1 rearrangements in breast-ovarian cancer families". Clin. Genet. 65 (2): 131–6. doi:10.1111/j.0009-9163.2004.00200.x. PMID 14984472.
  47. ↑ Hogervorst FB, Nederlof PM, Gille JJ, McElgunn CJ, Grippeling M, Pruntel R et al. (April 2003). "Large genomic deletions and duplications in the BRCA1 gene identified by a novel quantitative method". Cancer Res. 63 (7): 1449–53. PMID 12670888.
  48. ↑ Casilli F, Di Rocco ZC, Gad S, Tournier I, Stoppa-Lyonnet D, Frebourg T et al. (September 2002). "Rapid detection of novel BRCA1 rearrangements in high-risk breast-ovarian cancer families using multiplex PCR of short fluorescent fragments". Hum. Mutat. 20 (3): 218–26. doi:10.1002/humu.10108. PMID 12203994.
  49. ↑ Rouleau E, Lefol C, Tozlu S, Andrieu C, Guy C, Copigny F et al. (September 2007). "High-resolution oligonucleotide array-CGH applied to the detection and characterization of large rearrangements in the hereditary breast cancer gene BRCA1". Clin. Genet. 72 (3): 199–207. doi:10.1111/j.1399-0004.2007.00849.x. PMID 17718857.
  50. ↑ Tapia T, Smalley SV, Kohen P, Muñoz A, Solis LM, Corvalan A et al. (2008). "Promoter hypermethylation of BRCA1 correlates with absence of expression in hereditary breast cancer tumors". Epigenetics 3 (3): 157–63. doi:10.1186/bcr1858. PMID 18567944.
  51. ↑ Shen J, Ambrosone CB, Zhao H (March 2009). "Novel genetic variants in microRNA genes and familial breast cancer". Int. J. Cancer 124 (5): 1178–82. doi:10.1002/ijc.24008. PMID 19048628.
  52. ↑ Levin B, Lech D, Friedenson B (2012). "Evidence that BRCA1- or BRCA2-associated cancers are not inevitable". Mol Med 18 (9): 1327–37. doi:10.2119/molmed.2012.00280. PMC 3521784. PMID 22972572.
  53. ↑ 53.0 53.1 Lacroix M, Leclercq G (2005). "The "portrait" of hereditary breast cancer". Breast Cancer Research and Treatment 89 (3): 297–304. doi:10.1007/s10549-004-2172-4. PMID 15754129.
  54. ↑ 54.0 54.1 Struewing JP, Abeliovich D, Peretz T, Avishai N, Kaback MM, Collins FS et al. (1978). "Isolation of two human tumor epithelial cell lines from solid breast carcinomas". Journal of the National Cancer Institute 61 (2): 967–978. doi:10.1038/ng1095-198. PMID 7550349.
  55. ↑ 55.0 55.1 Tonin P, Serova O, Lenoir G, Lynch H, Durocher F, Simard J et al. (1995). "BRCA1 mutations in Ashkenazi Jewish women". American Journal of Human Genetics 57 (1): 189. PMC 1801236. PMID 7611288.
  56. ↑ Narod SA, Foulkes WD (2004). "BRCA1 and BRCA2: 1994 and beyond". Nature Reviews Cancer 4 (9): 665–676. doi:10.1038/nrc1431. PMID 15343273.
  57. ↑ den Dunnen JT, Antonarakis SE (2000). "Mutation nomenclature extensions and suggestions to describe complex mutations: a discussion". Human Mutation 15 (1): 7–12. doi:10.1002/(SICI)1098-1004(200001)15:1<7::AID-HUMU4>3.0.CO;2-N. PMID 10612815.
  58. ↑ 58.0 58.1 Neuhausen SL (2000). "Founder populations and their uses for breast cancer genetics". Cancer Research 2 (2): 77–81. doi:10.1186/bcr36. PMC 139426. PMID 11250694.
  59. ↑ Reeves MD, Yawitch TM, van der Merwe NC, van den Berg HJ, Dreyer G, van Rensburg EJ (July 2004). "BRCA1 mutations in South African breast and/or ovarian cancer families: evidence of a novel founder mutation in Afrikaner families". Int. J. Cancer 110 (5): 677–82. doi:10.1002/ijc.20186. PMID 15146556.
  60. ↑ Wagner TM, Möslinger RA, Muhr D, Langbauer G, Hirtenlehner K, Concin H et al. (1998). "BRCA1-related breast cancer in Austrian breast and ovarian cancer families: specific BRCA1 mutations and pathological characteristics". International Journal of Cancer 77 (3): 354–360. doi:10.1002/(SICI)1097-0215(19980729)77:3<354::AID-IJC8>3.0.CO;2-N. PMID 9663595.
  61. ↑ 61.0 61.1 Peelen T, van Vliet M, Petrij-Bosch A, Mieremet R, Szabo C, van den Ouweland AM et al. (1997). "A high proportion of novel mutations in BRCA1 with strong founder effects among Dutch and Belgian hereditary breast and ovarian cancer families". American Journal of Human Genetics 60 (5): 1041–1049. PMC 1712432. PMID 9150151.
  62. ↑ Claes K, Machackova E, De Vos M, Poppe B, De Paepe A, Messiaen L (1999). "Mutation analysis of the BRCA1 and BRCA2 genes in the Belgian patient population and identification of a Belgian founder mutation BRCA1 IVS5 + 3A > G". Disease Markers 15 (1–3): 69–73. doi:10.1155/1999/241046. PMC 3851655. PMID 10595255.
  63. ↑ Petrij-Bosch A, Peelen T, van Vliet M, van Eijk R, Olmer R, Drüsedau M et al. (1997). "BRCA1 genomic deletions are major founder mutations in Dutch breast cancer patients". Nature Genetics 17 (3): 341–345. doi:10.1038/ng1197-341. PMID 9354803.
  64. ↑ Verhoog LC, van den Ouweland AM, Berns E, van Veghel-Plandsoen MM, van Staveren IL, Wagner A et al. (2001). "Large regional differences in the frequency of distinct BRCA1/BRCA2 mutations in 517 Dutch breast and/or ovarian cancer families". European Journal of Cancer 37 (16): 2082–2090. doi:10.1016/S0959-8049(01)00244-1. PMID 11597388.
  65. ↑ Huusko P, Pääkkönen K, Launonen V, Pöyhönen M, Blanco G, Kauppila A et al. (1998). "Evidence of founder mutations in Finnish BRCA1 and BRCA2 families". American Journal of Human Genetics 62 (6): 1544–1548. doi:10.1086/301880. PMC 1377159. PMID 9585608.
  66. ↑ Pääkkönen K, Sauramo S, Sarantaus L, Vahteristo P, Hartikainen A, Vehmanen P et al. (2001). "Involvement of BRCA1 and BRCA2 in breast cancer in a western Finnish sub-population". Genetic Epidemiology 20 (2): 239–246. doi:10.1002/1098-2272(200102)20:2<239::AID-GEPI6>3.0.CO;2-Y. PMID 11180449.
  67. ↑ Muller D, Bonaiti-Pellié C, Abecassis J, Stoppa-Lyonnet D, Fricker JP (2004). "BRCA1 testing in breast and/or ovarian cancer families from northeastern France identifies two common mutations with a founder effect". Familial Cancer 3 (1): 15–20. doi:10.1023/B:FAME.0000026819.44213.df. PMID 15131401.
  68. ↑ Tonin PN, Mes-Masson AM, Narod SA, Ghadirian P, Provencher D (1999). "Founder BRCA1 and BRCA2 mutations in French Canadian ovarian cancer cases unselected for family history". Clinical Genetics 55 (5): 318–324. doi:10.1034/j.1399-0004.1999.550504.x. PMID 10422801.
  69. ↑ Backe J, Hofferbert S, Skawran B, Dörk T, Stuhrmann M, Karstens JH et al. (1999). "Frequency of BRCA1 mutation 5382insC in German breast cancer patients". Gynecologic Oncology 72 (3): 402–406. doi:10.1006/gyno.1998.5270. PMID 10053113.
  70. ↑ "Mutation data of the BRCA1 gene". KMDB/MutationView (Keio Mutation Databases). Keio University.
  71. ↑ Ladopoulou A, Kroupis C, Konstantopoulou I, Ioannidou-Mouzaka L, Schofield AC, Pantazidis A et al. (2002). "Germ line BRCA1 and BRCA2 mutations in Greek breast/ovarian cancer families: 5382insC is the most frequent mutation observed". Cancer Letters 185 (1): 61–70. doi:10.1016/S0304-3835(01)00845-X. PMID 12142080.
  72. ↑ Van Der Looij M, Szabo C, Besznyak I, Liszka G, Csokay B, Pulay T et al. (2000). "Prevalence of founder BRCA1 and BRCA2 mutations among breast and ovarian cancer patients in Hungary". International Journal of Cancer 86 (5): 737–740. doi:10.1002/(SICI)1097-0215(20000601)86:5<737::AID-IJC21>3.0.CO;2-1. PMID 10797299.
  73. ↑ Baudi F, Quaresima B, Grandinetti C, Cuda G, Faniello C, Tassone P et al. (2001). "Evidence of a founder mutation of BRCA1 in a highly homogeneous population from southern Italy with breast/ovarian cancer". Human Mutation 18 (2): 163–164. doi:10.1002/humu.1167. PMID 11462242.
  74. ↑ Sekine M, Nagata H, Tsuji S, Hirai Y, Fujimoto S, Hatae M et al. (2001). "Mutational analysis of BRCA1 and BRCA2 and clinicopathologic analysis of ovarian cancer in 82 ovarian cancer families: two common founder mutations of BRCA1 in Japanese population". Clinical Cancer Research 7 (10): 3144–3150. PMID 11595708.
  75. ↑ Liede A, Jack E, Hegele RA, Narod SA (2002). "A BRCA1 mutation in Native North American families". Human Mutation 19 (4): 460. doi:10.1002/humu.9027. PMID 11933205.
  76. ↑ 76.0 76.1 The Scottish/Northern Irish BRCA1/BRCA2, Consortium (2003). "BRCA1 and BRCA2 mutations in Scotland and Northern Ireland". British Journal of Cancer 88 (8): 1256–1262. doi:10.1038/sj.bjc.6600840. PMC 2747571. PMID 12698193.
  77. ↑ Borg A, Dørum A, Heimdal K, Maehle L, Hovig E, Møller P (1999). "BRCA1 1675delA and 1135insA account for one third of Norwegian familial breast-ovarian cancer and are associated with later disease onset than less frequent mutations". Disease Markers 15 (1–3): 79–84. doi:10.1155/1999/278269. PMC 3851406. PMID 10595257.
  78. ↑ Heimdal K, Maehle L, Apold J, Pedersen JC, Møller P (2003). "The Norwegian founder mutations in BRCA1: high penetrance confirmed in an incident cancer series and differences observed in the risk of ovarian cancer". Europen Journal of Cancer 39 (15): 2205–2213. doi:10.1016/S0959-8049(03)00548-3. PMID 14522380.
  79. ↑ Liede A, Malik IA, Aziz Z, Rios Pd Pde L, Kwan E, Narod SA (2002). "Contribution of BRCA1 and BRCA2 Mutations to Breast and Ovarian Cancer in Pakistan". American Journal of Human Genetics 71 (3): 595–606. doi:10.1086/342506. PMC 379195. PMID 12181777.
  80. ↑ Górski B, Byrski T, Huzarski T, Jakubowska A, Menkiszak J, Gronwald J et al. (2000). "Founder mutations in the BRCA1 gene in Polish families with breast-ovarian cancer". American Journal of Human Genetics 66 (6): 1963–1968. doi:10.1086/302922. PMC 1378051. PMID 10788334.
  81. ↑ Perkowska M, BroZek I, Wysocka B, Haraldsson K, Sandberg T, Johansson U et al. (May 2003). "BRCA1 and BRCA2 mutation analysis in breast-ovarian cancer families from northeastern Poland". Hum. Mutat. 21 (5): 553–4. doi:10.1002/humu.9139. PMID 12673801.
  82. ↑ Gayther SA, Harrington P, Russell P, Kharkevich G, Garkavtseva RF, Ponder BA (May 1997). "Frequently occurring germ-line mutations of the BRCA1 gene in ovarian cancer families from Russia". Am. J. Hum. Genet. 60 (5): 1239–42. PMC 1712436. PMID 9150173.
  83. ↑ Liede A, Cohen B, Black DM, Davidson RH, Renwick A, Hoodfar E et al. (February 2000). "Evidence of a founder BRCA1 mutation in Scotland". Br. J. Cancer 82 (3): 705–11. doi:10.1054/bjoc.1999.0984. PMC 2363321. PMID 10682686.
  84. ↑ Vega A, Campos B, Bressac-De-Paillerets B, Bond PM, Janin N, Douglas FS et al. (June 2001). "The R71G BRCA1 is a founder Spanish mutation and leads to aberrant splicing of the transcript". Hum. Mutat. 17 (6): 520–1. doi:10.1002/humu.1136. PMID 11385711.
  85. ↑ Campos B, Díez O, Odefrey F, Domènech M, Moncoutier V, Martínez-Ferrandis JI et al. (April 2003). "Haplotype analysis of the BRCA2 9254delATCAT recurrent mutation in breast/ovarian cancer families from Spain". Hum. Mutat. 21 (4): 452. doi:10.1002/humu.9133. PMID 12655574.
  86. ↑ Bergman A, Einbeigi Z, Olofsson U, Taib Z, Wallgren A, Karlsson P et al. (October 2001). "The western Swedish BRCA1 founder mutation 3171ins5; a 3.7 cM conserved haplotype of today is a reminiscence of a 1500-year-old mutation". Eur. J. Hum. Genet. 9 (10): 787–93. doi:10.1038/sj.ejhg.5200704. PMID 11781691.
  87. ↑ Hansen KR, Knowlton NS, Thyer AC, Charleston JS, Soules MR, Klein NA (March 2008). "A new model of reproductive aging: the decline in ovarian non-growing follicle number from birth to menopause". Hum. Reprod. 23 (3): 699–708. doi:10.1093/humrep/dem408. PMID 18192670.
  88. ↑ Oktay K, Kim JY, Barad D, Babayev SN (January 2010). "Association of BRCA1 mutations with occult primary ovarian insufficiency: a possible explanation for the link between infertility and breast/ovarian cancer risks". J. Clin. Oncol. 28 (2): 240–4. doi:10.1200/JCO.2009.24.2057. PMC 3040011. PMID 19996028.
  89. ↑ Rzepka-Górska I, Tarnowski B, Chudecka-Głaz A, Górski B, Zielińska D, Tołoczko-Grabarek A (November 2006). "Premature menopause in patients with BRCA1 gene mutation". Breast Cancer Res. Treat. 100 (1): 59–63. doi:10.1007/s10549-006-9220-1. PMID 16773440.
  90. ↑ 90.0 90.1 Titus S, Li F, Stobezki R, Akula K, Unsal E, Jeong K et al. (February 2013). "Impairment of BRCA1-related DNA double-strand break repair leads to ovarian aging in mice and humans". Sci Transl Med 5 (172): 172ra21. doi:10.1126/scitranslmed.3004925. PMID 23408054.
  91. ↑ Bernstein H, Bernstein C, Michod RE (2011). "Chapter 19: Meiosis as an Evolutionary Adaptation for DNA Repair". In Kruman I. DNA Repair. Intech. doi:10.5772/25117. ISBN 978-953-307-697-3.
  92. ↑ 92.0 92.1 Taron M, Rosell R, Felip E, Mendez P, Souglakos J, Ronco MS et al. (October 2004). "BRCA1 mRNA expression levels as an indicator of chemoresistance in lung cancer". Hum. Mol. Genet. 13 (20): 2443–9. doi:10.1093/hmg/ddh260. PMID 15317748.
  93. ↑ 93.0 93.1 Papadaki C, Sfakianaki M, Ioannidis G, Lagoudaki E, Trypaki M, Tryfonidis K et al. (April 2012). "ERCC1 and BRAC1 mRNA expression levels in the primary tumor could predict the effectiveness of the second-line cisplatin-based chemotherapy in pretreated patients with metastatic non-small cell lung cancer". J Thorac Oncol 7 (4): 663–71. doi:10.1097/JTO.0b013e318244bdd4. PMID 22425915.
  94. ↑ Weberpals J, Garbuio K, O'Brien A, Clark-Knowles K, Doucette S, Antoniouk O et al. (February 2009). "The DNA repair proteins BRCA1 and ERCC1 as predictive markers in sporadic ovarian cancer". Int. J. Cancer 124 (4): 806–15. doi:10.1002/ijc.23987. PMID 19035454.
  95. ↑ Robert Cook-Deegan, MD et al (2010) Impact of Gene Patents and Licensing Practices on Access to Genetic Testing for Inherited Susceptibility to Cancer: Comparing Breast and Ovarian Cancers to Colon Cancers: Patents and Licensing for Breast, Ovarian and Colon Cancer Testing Genet Med.12(4 Suppl): S15–S38.
  96. ↑ Benowitz S (January 2003). "European groups oppose Myriad's latest patent on BRCA1". J. Natl. Cancer Inst. 95 (1): 8–9. doi:10.1093/jnci/95.1.8. PMID 12509391.
  97. ↑ Conley J, Vorhous D, Cook-Deegan J (2011-03-01). "How Will Myriad Respond to the Next Generation of BRCA Testing?". Robinson, Bradshaw, and Hinson. Retrieved 2012-12-09.
  98. ↑ "Genetics and Patenting". Human Genome Project Information. U.S. Department of Energy Genome Programs. 2010-07-07.
  99. ↑ Liptak, Adam (June 13, 2013). "Supreme Court Rules Human Genes May Not Be Patented". New York Times. Retrieved June 13, 2013.
  100. ↑ Corderoy, Amy (February 15, 2013). "Landmark patent ruling over breast cancer gene BRCA1". Sydney Morning Herald. Retrieved June 14, 2013.
  101. ↑ "Australian federal court rules isolated genetic material can be patented". The Guardian. 5 September 2014. Retrieved 14 September 2014.
  102. ↑ Foray N, Marot D, Randrianarison V, Venezia ND, Picard D, Perricaudet M et al. (June 2002). "Constitutive association of BRCA1 and c-Abl and its ATM-dependent disruption after irradiation". Mol. Cell. Biol. 22 (12): 4020–32. doi:10.1128/MCB.22.12.4020-4032.2002. PMC 133860. PMID 12024016.
  103. ↑ Altiok S, Batt D, Altiok N, Papautsky A, Downward J, Roberts TM et al. (November 1999). "Heregulin induces phosphorylation of BRCA1 through phosphatidylinositol 3-Kinase/AKT in breast cancer cells". J. Biol. Chem. 274 (45): 32274–8. doi:10.1074/jbc.274.45.32274. PMID 10542266.
  104. ↑ Xiang T, Ohashi A, Huang Y, Pandita TK, Ludwig T, Powell SN et al. (December 2008). "Negative Regulation of AKT Activation by BRCA1". Cancer Res. 68 (24): 10040–4. doi:10.1158/0008-5472.CAN-08-3009. PMC 2605656. PMID 19074868.
  105. ↑ Yeh S, Hu YC, Rahman M, Lin HK, Hsu CL, Ting HJ et al. (October 2000). "Increase of androgen-induced cell death and androgen receptor transactivation by BRCA1 in prostate cancer cells". Proc. Natl. Acad. Sci. U.S.A. 97 (21): 11256–61. doi:10.1073/pnas.190353897. PMC 17187. PMID 11016951.
  106. ↑ 107.0 107.1 Kim ST, Lim DS, Canman CE, Kastan MB (December 1999). "Substrate specificities and identification of putative substrates of ATM kinase family members". J. Biol. Chem. 274 (53): 37538–43. doi:10.1074/jbc.274.53.37538. PMID 10608806.
  107. ↑ 108.0 108.1 Tibbetts RS, Cortez D, Brumbaugh KM, Scully R, Livingston D, Elledge SJ et al. (December 2000). "Functional interactions between BRCA1 and the checkpoint kinase ATR during genotoxic stress". Genes Dev. 14 (23): 2989–3002. doi:10.1101/gad.851000. PMC 317107. PMID 11114888.
  108. ↑ 109.0 109.1 Chen J (September 2000). "Ataxia telangiectasia-related protein is involved in the phosphorylation of BRCA1 following deoxyribonucleic acid damage". Cancer Res. 60 (18): 5037–9. PMID 11016625.
  109. ↑ 110.0 110.1 Gatei M, Zhou BB, Hobson K, Scott S, Young D, Khanna KK (May 2001). "Ataxia telangiectasia mutated (ATM) kinase and ATM and Rad3 related kinase mediate phosphorylation of Brca1 at distinct and overlapping sites. In vivo assessment using phospho-specific antibodies". J. Biol. Chem. 276 (20): 17276–80. doi:10.1074/jbc.M011681200. PMID 11278964.
  110. ↑ Gatei M, Scott SP, Filippovitch I, Soronika N, Lavin MF, Weber B et al. (June 2000). "Role for ATM in DNA damage-induced phosphorylation of BRCA1". Cancer Res. 60 (12): 3299–304. PMID 10866324.
  111. ↑ Cortez D, Wang Y, Qin J, Elledge SJ (November 1999). "Requirement of ATM-dependent phosphorylation of brca1 in the DNA damage response to double-strand breaks". Science 286 (5442): 1162–6. doi:10.1126/science.286.5442.1162. PMID 10550055.
  112. ↑ Houvras Y, Benezra M, Zhang H, Manfredi JJ, Weber BL, Licht JD (November 2000). "BRCA1 physically and functionally interacts with ATF1". J. Biol. Chem. 275 (46): 36230–7. doi:10.1074/jbc.M002539200. PMID 10945975.
  113. ↑ Ouchi M, Fujiuchi N, Sasai K, Katayama H, Minamishima YA, Ongusaha PP et al. (May 2004). "BRCA1 phosphorylation by Aurora-A in the regulation of G2 to M transition". J. Biol. Chem. 279 (19): 19643–8. doi:10.1074/jbc.M311780200. PMID 14990569.
  114. ↑ 115.0 115.1 Cantor SB, Bell DW, Ganesan S, Kass EM, Drapkin R, Grossman S et al. (April 2001). "BACH1, a novel helicase-like protein, interacts directly with BRCA1 and contributes to its DNA repair function". Cell 105 (1): 149–60. doi:10.1016/S0092-8674(01)00304-X. PMID 11301010.
  115. ↑ 116.0 116.1 116.2 Mallery DL, Vandenberg CJ, Hiom K (December 2002). "Activation of the E3 ligase function of the BRCA1/BARD1 complex by polyubiquitin chains". EMBO J. 21 (24): 6755–62. doi:10.1093/emboj/cdf691. PMC 139111. PMID 12485996.
  116. ↑ 117.0 117.1 Brzovic PS, Keeffe JR, Nishikawa H, Miyamoto K, Fox D, Fukuda M et al. (May 2003). "Binding and recognition in the assembly of an active BRCA1/BARD1 ubiquitin-ligase complex". Proc. Natl. Acad. Sci. U.S.A. 100 (10): 5646–51. doi:10.1073/pnas.0836054100. PMC 156255. PMID 12732733.
  117. ↑ 118.0 118.1 Nishikawa H, Ooka S, Sato K, Arima K, Okamoto J, Klevit RE et al. (February 2004). "Mass spectrometric and mutational analyses reveal Lys-6-linked polyubiquitin chains catalyzed by BRCA1-BARD1 ubiquitin ligase". J. Biol. Chem. 279 (6): 3916–24. doi:10.1074/jbc.M308540200. PMID 14638690.
  118. ↑ 119.0 119.1 Kentsis A, Gordon RE, Borden KL (November 2002). "Control of biochemical reactions through supramolecular RING domain self-assembly". Proc. Natl. Acad. Sci. U.S.A. 99 (24): 15404–9. doi:10.1073/pnas.202608799. PMC 137729. PMID 12438698.
  119. ↑ 120.0 120.1 120.2 Chen A, Kleiman FE, Manley JL, Ouchi T, Pan ZQ (June 2002). "Autoubiquitination of the BRCA1*BARD1 RING ubiquitin ligase". J. Biol. Chem. 277 (24): 22085–92. doi:10.1074/jbc.M201252200. PMID 11927591.
  120. ↑ 121.0 121.1 121.2 121.3 121.4 121.5 121.6 Dong Y, Hakimi MA, Chen X, Kumaraswamy E, Cooch NS, Godwin AK et al. (November 2003). "Regulation of BRCC, a holoenzyme complex containing BRCA1 and BRCA2, by a signalosome-like subunit and its role in DNA repair". Mol. Cell 12 (5): 1087–99. doi:10.1016/S1097-2765(03)00424-6. PMID 14636569.
  121. ↑ 122.0 122.1 122.2 Sato K, Hayami R, Wu W, Nishikawa T, Nishikawa H, Okuda Y et al. (July 2004). "Nucleophosmin/B23 is a candidate substrate for the BRCA1-BARD1 ubiquitin ligase". J. Biol. Chem. 279 (30): 30919–22. doi:10.1074/jbc.C400169200. PMID 15184379.
  122. ↑ 123.0 123.1 123.2 Vandenberg CJ, Gergely F, Ong CY, Pace P, Mallery DL, Hiom K et al. (July 2003). "BRCA1-independent ubiquitination of FANCD2". Mol. Cell 12 (1): 247–54. doi:10.1016/S1097-2765(03)00281-8. PMID 12887909.
  123. ↑ 124.0 124.1 Wu-Baer F, Lagrazon K, Yuan W, Baer R (September 2003). "The BRCA1/BARD1 heterodimer assembles polyubiquitin chains through an unconventional linkage involving lysine residue K6 of ubiquitin". J. Biol. Chem. 278 (37): 34743–6. doi:10.1074/jbc.C300249200. PMID 12890688.
  124. ↑ 125.0 125.1 Hashizume R, Fukuda M, Maeda I, Nishikawa H, Oyake D, Yabuki Y et al. (May 2001). "The RING heterodimer BRCA1-BARD1 is a ubiquitin ligase inactivated by a breast cancer-derived mutation". J. Biol. Chem. 276 (18): 14537–40. doi:10.1074/jbc.C000881200. PMID 11278247.
  125. ↑ 126.0 126.1 Kleiman FE, Manley JL (March 2001). "The BARD1-CstF-50 interaction links mRNA 3' end formation to DNA damage and tumor suppression". Cell 104 (5): 743–53. doi:10.1016/S0092-8674(01)00270-7. PMID 11257228.
  126. ↑ 127.0 127.1 Kleiman FE, Manley JL (September 1999). "Functional interaction of BRCA1-associated BARD1 with polyadenylation factor CstF-50". Science 285 (5433): 1576–9. doi:10.1126/science.285.5433.1576. PMID 10477523.
  127. ↑ Wu LC, Wang ZW, Tsan JT, Spillman MA, Phung A, Xu XL et al. (December 1996). "Identification of a RING protein that can interact in vivo with the BRCA1 gene product". Nat. Genet. 14 (4): 430–40. doi:10.1038/ng1296-430. PMID 8944023.
  128. ↑ Fabbro M, Rodriguez JA, Baer R, Henderson BR (June 2002). "BARD1 induces BRCA1 intranuclear foci formation by increasing RING-dependent BRCA1 nuclear import and inhibiting BRCA1 nuclear export". J. Biol. Chem. 277 (24): 21315–24. doi:10.1074/jbc.M200769200. PMID 11925436.
  129. ↑ Rodriguez JA, Schüchner S, Au WW, Fabbro M, Henderson BR (March 2004). "Nuclear-cytoplasmic shuttling of BARD1 contributes to its proapoptotic activity and is regulated by dimerization with BRCA1". Oncogene 23 (10): 1809–20. doi:10.1038/sj.onc.1207302. PMID 14647430.
  130. ↑ 131.0 131.1 131.2 131.3 131.4 131.5 Chiba N, Parvin JD (October 2001). "Redistribution of BRCA1 among four different protein complexes following replication blockage". J. Biol. Chem. 276 (42): 38549–54. doi:10.1074/jbc.M105227200. PMID 11504724.
  131. ↑ Morris JR, Keep NH, Solomon E (March 2002). "Identification of residues required for the interaction of BARD1 with BRCA1". J. Biol. Chem. 277 (11): 9382–6. doi:10.1074/jbc.M109249200. PMID 11773071.
  132. ↑ Brzovic PS, Meza JE, King MC, Klevit RE (November 2001). "BRCA1 RING domain cancer-predisposing mutations. Structural consequences and effects on protein-protein interactions". J. Biol. Chem. 276 (44): 41399–406. doi:10.1074/jbc.M106551200. PMID 11526114.
  133. ↑ Xia Y, Pao GM, Chen HW, Verma IM, Hunter T (February 2003). "Enhancement of BRCA1 E3 ubiquitin ligase activity through direct interaction with the BARD1 protein". J. Biol. Chem. 278 (7): 5255–63. doi:10.1074/jbc.M204591200. PMID 12431996.
  134. ↑ Meza JE, Brzovic PS, King MC, Klevit RE (February 1999). "Mapping the functional domains of BRCA1. Interaction of the ring finger domains of BRCA1 and BARD1". J. Biol. Chem. 274 (9): 5659–65. doi:10.1074/jbc.274.9.5659. PMID 10026184.
  135. ↑ Fabbro M, Savage K, Hobson K, Deans AJ, Powell SN, McArthur GA et al. (July 2004). "BRCA1-BARD1 complexes are required for p53Ser-15 phosphorylation and a G1/S arrest following ionizing radiation-induced DNA damage". J. Biol. Chem. 279 (30): 31251–8. doi:10.1074/jbc.M405372200. PMID 15159397.
  136. ↑ 137.0 137.1 Yu X, Wu LC, Bowcock AM, Aronheim A, Baer R (September 1998). "The C-terminal (BRCT) domains of BRCA1 interact in vivo with CtIP, a protein implicated in the CtBP pathway of transcriptional repression". J. Biol. Chem. 273 (39): 25388–92. doi:10.1074/jbc.273.39.25388. PMID 9738006.
  137. ↑ Jin Y, Xu XL, Yang MC, Wei F, Ayi TC, Bowcock AM et al. (October 1997). "Cell cycle-dependent colocalization of BARD1 and BRCA1 proteins in discrete nuclear domains". Proc. Natl. Acad. Sci. U.S.A. 94 (22): 12075–80. doi:10.1073/pnas.94.22.12075. PMC 23707. PMID 9342365.
  138. ↑ Scully R, Ganesan S, Vlasakova K, Chen J, Socolovsky M, Livingston DM (December 1999). "Genetic analysis of BRCA1 function in a defined tumor cell line". Mol. Cell 4 (6): 1093–9. doi:10.1016/S1097-2765(00)80238-5. PMID 10635334.
  139. ↑ Tascou S, Kang TW, Trappe R, Engel W, Burfeind P (September 2003). "Identification and characterization of NIF3L1 BP1, a novel cytoplasmic interaction partner of the NIF3L1 protein". Biochem. Biophys. Res. Commun. 309 (2): 440–8. doi:10.1016/j.bbrc.2003.07.008. PMID 12951069.
  140. ↑ 141.0 141.1 141.2 Benezra M, Chevallier N, Morrison DJ, MacLachlan TK, El-Deiry WS, Licht JD (July 2003). "BRCA1 augments transcription by the NF-kappaB transcription factor by binding to the Rel domain of the p65/RelA subunit". J. Biol. Chem. 278 (29): 26333–41. doi:10.1074/jbc.M303076200. PMID 12700228.
  141. ↑ Ryser S, Dizin E, Jefford CE, Delaval B, Gagos S, Christodoulidou A et al. (February 2009). "Distinct roles of BARD1 isoforms in mitosis: full-length BARD1 mediates Aurora B degradation, cancer-associated BARD1beta scaffolds Aurora B and BRCA2". Cancer Res. 69 (3): 1125–34. doi:10.1158/0008-5472.CAN-08-2134. PMID 19176389.
  142. ↑ Nishikawa H, Wu W, Koike A, Kojima R, Gomi H, Fukuda M et al. (January 2009). "BRCA1-associated protein 1 interferes with BRCA1/BARD1 RING heterodimer activity". Cancer Res. 69 (1): 111–9. doi:10.1158/0008-5472.CAN-08-3355. PMID 19117993.
  143. ↑ 144.0 144.1 Chen J, Silver DP, Walpita D, Cantor SB, Gazdar AF, Tomlinson G et al. (September 1998). "Stable interaction between the products of the BRCA1 and BRCA2 tumor suppressor genes in mitotic and meiotic cells". Mol. Cell 2 (3): 317–28. doi:10.1016/S1097-2765(00)80276-2. PMID 9774970.
  144. ↑ 145.0 145.1 Reuter TY, Medhurst AL, Waisfisz Q, Zhi Y, Herterich S, Hoehn H et al. (October 2003). "Yeast two-hybrid screens imply involvement of Fanconi anemia proteins in transcription regulation, cell signaling, oxidative metabolism, and cellular transport". Exp. Cell Res. 289 (2): 211–21. doi:10.1016/S0014-4827(03)00261-1. PMID 14499622.
  145. ↑ Sarkisian CJ, Master SR, Huber LJ, Ha SI, Chodosh LA (October 2001). "Analysis of murine Brca2 reveals conservation of protein-protein interactions but differences in nuclear localization signals". J. Biol. Chem. 276 (40): 37640–8. doi:10.1074/jbc.M106281200. PMID 11477095.
  146. ↑ 147.0 147.1 147.2 147.3 Rodriguez M, Yu X, Chen J, Songyang Z (December 2003). "Phosphopeptide binding specificities of BRCA1 COOH-terminal (BRCT) domains". J. Biol. Chem. 278 (52): 52914–8. doi:10.1074/jbc.C300407200. PMID 14578343.
  147. ↑ 148.0 148.1 148.2 148.3 Wada O, Oishi H, Takada I, Yanagisawa J, Yano T, Kato S (August 2004). "BRCA1 function mediates a TRAP/DRIP complex through direct interaction with TRAP220". Oncogene 23 (35): 6000–5. doi:10.1038/sj.onc.1207786. PMID 15208681.
  148. ↑ Botuyan MV, Nominé Y, Yu X, Juranic N, Macura S, Chen J et al. (July 2004). "Structural basis of BACH1 phosphopeptide recognition by BRCA1 tandem BRCT domains". Structure 12 (7): 1137–46. doi:10.1016/j.str.2004.06.002. PMC 3652423. PMID 15242590.
  149. ↑ Yu X, Chini CC, He M, Mer G, Chen J (October 2003). "The BRCT domain is a phospho-protein binding domain". Science 302 (5645): 639–42. doi:10.1126/science.1088753. PMID 14576433.
  150. ↑ Clapperton JA, Manke IA, Lowery DM, Ho T, Haire LF, Yaffe MB et al. (June 2004). "Structure and mechanism of BRCA1 BRCT domain recognition of phosphorylated BACH1 with implications for cancer". Nature Structural & Molecular Biology 11 (6): 512–8. doi:10.1038/nsmb775. PMID 15133502.
  151. ↑ 152.0 152.1 152.2 Hu YF, Li R (June 2002). "JunB potentiates function of BRCA1 activation domain 1 (AD1) through a coiled-coil-mediated interaction". Genes Dev. 16 (12): 1509–17. doi:10.1101/gad.995502. PMC 186344. PMID 12080089.
  152. ↑ Lee JS, Collins KM, Brown AL, Lee CH, Chung JH (March 2000). "hCds1-mediated phosphorylation of BRCA1 regulates the DNA damage response". Nature 404 (6774): 201–4. doi:10.1038/35004614. PMID 10724175.
  153. ↑ Chabalier-Taste C, Racca C, Dozier C, Larminat F (December 2008). "BRCA1 is regulated by Chk2 in response to spindle damage". Biochim. Biophys. Acta 1783 (12): 2223–33. doi:10.1016/j.bbamcr.2008.08.006. PMID 18804494.
  154. ↑ Lin SY, Li K, Stewart GS, Elledge SJ (April 2004). "Human Claspin works with BRCA1 to both positively and negatively regulate cell proliferation". Proc. Natl. Acad. Sci. U.S.A. 101 (17): 6484–9. doi:10.1073/pnas.0401847101. PMC 404071. PMID 15096610.
  155. ↑ Ye Q, Hu YF, Zhong H, Nye AC, Belmont AS, Li R (December 2001). "BRCA1-induced large-scale chromatin unfolding and allele-specific effects of cancer-predisposing mutations". J. Cell Biol. 155 (6): 911–21. doi:10.1083/jcb.200108049. PMC 2150890. PMID 11739404.
  156. ↑ 157.0 157.1 Pao GM, Janknecht R, Ruffner H, Hunter T, Verma IM (February 2000). "CBP/p300 interact with and function as transcriptional coactivators of BRCA1". Proc. Natl. Acad. Sci. U.S.A. 97 (3): 1020–5. doi:10.1073/pnas.97.3.1020. PMC 15508. PMID 10655477.
  157. ↑ 158.0 158.1 Chai YL, Cui J, Shao N, Shyam E, Reddy P, Rao VN (January 1999). "The second BRCT domain of BRCA1 proteins interacts with p53 and stimulates transcription from the p21WAF1/CIP1 promoter". Oncogene 18 (1): 263–8. doi:10.1038/sj.onc.1202323. PMID 9926942.
  158. ↑ 159.0 159.1 159.2 Fan S, Ma YX, Wang C, Yuan RQ, Meng Q, Wang JA et al. (January 2002). "p300 Modulates the BRCA1 inhibition of estrogen receptor activity". Cancer Res. 62 (1): 141–51. PMID 11782371.
  159. ↑ Neish AS, Anderson SF, Schlegel BP, Wei W, Parvin JD (February 1998). "Factors associated with the mammalian RNA polymerase II holoenzyme". Nucleic Acids Res. 26 (3): 847–53. doi:10.1093/nar/26.3.847. PMC 147327. PMID 9443979.
  160. ↑ O'Brien KA, Lemke SJ, Cocke KS, Rao RN, Beckmann RP (July 1999). "Casein kinase 2 binds to and phosphorylates BRCA1". Biochem. Biophys. Res. Commun. 260 (3): 658–64. doi:10.1006/bbrc.1999.0892. PMID 10403822.
  161. ↑ Chen Y, Farmer AA, Chen CF, Jones DC, Chen PL, Lee WH (July 1996). "BRCA1 is a 220-kDa nuclear phosphoprotein that is expressed and phosphorylated in a cell cycle-dependent manner". Cancer Res. 56 (14): 3168–72. PMID 8764100.
  162. ↑ Ruffner H, Jiang W, Craig AG, Hunter T, Verma IM (July 1999). "BRCA1 is phosphorylated at serine 1497 in vivo at a cyclin-dependent kinase 2 phosphorylation site". Mol. Cell. Biol. 19 (7): 4843–54. PMC 84283. PMID 10373534.
  163. ↑ Schlegel BP, Starita LM, Parvin JD (February 2003). "Overexpression of a protein fragment of RNA helicase A causes inhibition of endogenous BRCA1 function and defects in ploidy and cytokinesis in mammary epithelial cells". Oncogene 22 (7): 983–91. doi:10.1038/sj.onc.1206195. PMID 12592385.
  164. ↑ Anderson SF, Schlegel BP, Nakajima T, Wolpin ES, Parvin JD (July 1998). "BRCA1 protein is linked to the RNA polymerase II holoenzyme complex via RNA helicase A". Nat. Genet. 19 (3): 254–6. doi:10.1038/930. PMID 9662397.
  165. ↑ Chai Y, Chipitsyna G, Cui J, Liao B, Liu S, Aysola K et al. (March 2001). "c-Fos oncogene regulator Elk-1 interacts with BRCA1 splice variants BRCA1a/1b and enhances BRCA1a/1b-mediated growth suppression in breast cancer cells". Oncogene 20 (11): 1357–67. doi:10.1038/sj.onc.1204256. PMID 11313879.
  166. ↑ Zheng L, Annab LA, Afshari CA, Lee WH, Boyer TG (August 2001). "BRCA1 mediates ligand-independent transcriptional repression of the estrogen receptor". Proc. Natl. Acad. Sci. U.S.A. 98 (17): 9587–92. doi:10.1073/pnas.171174298. PMC 55496. PMID 11493692.
  167. ↑ Fan S, Ma YX, Wang C, Yuan RQ, Meng Q, Wang JA et al. (January 2001). "Role of direct interaction in BRCA1 inhibition of estrogen receptor activity". Oncogene 20 (1): 77–87. doi:10.1038/sj.onc.1204073. PMID 11244506.
  168. ↑ Kawai H, Li H, Chun P, Avraham S, Avraham HK (October 2002). "Direct interaction between BRCA1 and the estrogen receptor regulates vascular endothelial growth factor (VEGF) transcription and secretion in breast cancer cells". Oncogene 21 (50): 7730–9. doi:10.1038/sj.onc.1205971. PMID 12400015.
  169. ↑ Folias A, Matkovic M, Bruun D, Reid S, Hejna J, Grompe M et al. (October 2002). "BRCA1 interacts directly with the Fanconi anemia protein FANCA". Hum. Mol. Genet. 11 (21): 2591–7. doi:10.1093/hmg/11.21.2591. PMID 12354784.
  170. ↑ Yan J, Zhu J, Zhong H, Lu Q, Huang C, Ye Q (October 2003). "BRCA1 interacts with FHL2 and enhances FHL2 transactivation function". FEBS Lett. 553 (1–2): 183–9. doi:10.1016/S0014-5793(03)00978-5. PMID 14550570.
  171. ↑ Yan JH, Ye QN, Zhu JH, Zhong HJ, Zheng HY, Huang CF (December 2003). "[Isolation and characterization of a BRCA1-interacting protein]". Yi Chuan Xue Bao (in Chinese) 30 (12): 1161–6. PMID 14986435.
  172. ↑ Paull TT, Rogakou EP, Yamazaki V, Kirchgessner CU, Gellert M, Bonner WM (2000). "A critical role for histone H2AX in recruitment of repair factors to nuclear foci after DNA damage". Curr. Biol. 10 (15): 886–95. doi:10.1016/S0960-9822(00)00610-2. PMID 10959836.
  173. ↑ Sutherland KD, Visvader JE, Choong DY, Sum EY, Lindeman GJ, Campbell IG (October 2003). "Mutational analysis of the LMO4 gene, encoding a BRCA1-interacting protein, in breast carcinomas". Int. J. Cancer 107 (1): 155–8. doi:10.1002/ijc.11343. PMID 12925972.
  174. ↑ Sum EY, Peng B, Yu X, Chen J, Byrne J, Lindeman GJ et al. (March 2002). "The LIM domain protein LMO4 interacts with the cofactor CtIP and the tumor suppressor BRCA1 and inhibits BRCA1 activity". J. Biol. Chem. 277 (10): 7849–56. doi:10.1074/jbc.M110603200. PMID 11751867.
  175. ↑ Gilmore PM, McCabe N, Quinn JE, Kennedy RD, Gorski JJ, Andrews HN et al. (June 2004). "BRCA1 interacts with and is required for paclitaxel-induced activation of mitogen-activated protein kinase kinase kinase 3". Cancer Res. 64 (12): 4148–54. doi:10.1158/0008-5472.CAN-03-4080. PMID 15205325.
  176. ↑ Chiba N, Parvin JD (August 2002). "The BRCA1 and BARD1 association with the RNA polymerase II holoenzyme". Cancer Res. 62 (15): 4222–8. PMID 12154023.
  177. ↑ 178.0 178.1 Scully R, Anderson SF, Chao DM, Wei W, Ye L, Young RA et al. (May 1997). "BRCA1 is a component of the RNA polymerase II holoenzyme". Proc. Natl. Acad. Sci. U.S.A. 94 (11): 5605–10. doi:10.1073/pnas.94.11.5605. PMC 20825. PMID 9159119.
  178. ↑ 179.0 179.1 179.2 Zhong Q, Chen CF, Li S, Chen Y, Wang CC, Xiao J et al. (July 1999). "Association of BRCA1 with the hRad50-hMre11-p95 complex and the DNA damage response". Science 285 (5428): 747–50. doi:10.1126/science.285.5428.747. PMID 10426999.
  179. ↑ Paull TT, Cortez D, Bowers B, Elledge SJ, Gellert M (May 2001). "Direct DNA binding by Brca1". Proc. Natl. Acad. Sci. U.S.A. 98 (11): 6086–91. doi:10.1073/pnas.111125998. PMC 33426. PMID 11353843.
  180. ↑ 181.0 181.1 Li H, Lee TH, Avraham H (June 2002). "A novel tricomplex of BRCA1, Nmi, and c-Myc inhibits c-Myc-induced human telomerase reverse transcriptase gene (hTERT) promoter activity in breast cancer". J. Biol. Chem. 277 (23): 20965–73. doi:10.1074/jbc.M112231200. PMID 11916966.
  181. ↑ Xiong J, Fan S, Meng Q, Schramm L, Wang C, Bouzahza B et al. (December 2003). "BRCA1 inhibition of telomerase activity in cultured cells". Mol. Cell. Biol. 23 (23): 8668–90. doi:10.1128/MCB.23.23.8668-8690.2003. PMC 262673. PMID 14612409.
  182. ↑ Zhou C, Liu J (March 2003). "Inhibition of human telomerase reverse transcriptase gene expression by BRCA1 in human ovarian cancer cells". Biochem. Biophys. Res. Commun. 303 (1): 130–6. doi:10.1016/S0006-291X(03)00318-8. PMID 12646176.
  183. ↑ Park JJ, Irvine RA, Buchanan G, Koh SS, Park JM, Tilley WD et al. (November 2000). "Breast cancer susceptibility gene 1 (BRCAI) is a coactivator of the androgen receptor". Cancer Res. 60 (21): 5946–9. PMID 11085509.
  184. ↑ Cabart P, Chew HK, Murphy S (July 2004). "BRCA1 cooperates with NUFIP and P-TEFb to activate transcription by RNA polymerase II". Oncogene 23 (31): 5316–29. doi:10.1038/sj.onc.1207684. PMID 15107825.
  185. ↑ Abramovitch S, Werner H (2003). "Functional and physical interactions between BRCA1 and p53 in transcriptional regulation of the IGF-IR gene". Horm. Metab. Res. 35 (11–12): 758–62. doi:10.1055/s-2004-814154. PMID 14710355.
  186. ↑ Ouchi T, Monteiro AN, August A, Aaronson SA, Hanafusa H (March 1998). "BRCA1 regulates p53-dependent gene expression". Proc. Natl. Acad. Sci. U.S.A. 95 (5): 2302–6. doi:10.1073/pnas.95.5.2302. PMC 19327. PMID 9482880.
  187. ↑ Zhang H, Somasundaram K, Peng Y, Tian H, Zhang H, Bi D et al. (April 1998). "BRCA1 physically associates with p53 and stimulates its transcriptional activity". Oncogene 16 (13): 1713–21. doi:10.1038/sj.onc.1201932. PMID 9582019.
  188. ↑ Sy SM, Huen MS, Chen J (April 2009). "PALB2 is an integral component of the BRCA complex required for homologous recombination repair". Proc. Natl. Acad. Sci. U.S.A. 106 (17): 7155–60. doi:10.1073/pnas.0811159106. PMC 2678481. PMID 19369211.
  189. ↑ Krum SA, Miranda GA, Lin C, Lane TF (December 2003). "BRCA1 associates with processive RNA polymerase II". J. Biol. Chem. 278 (52): 52012–20. doi:10.1074/jbc.M308418200. PMID 14506230.
  190. ↑ Krum SA, Womack JE, Lane TF (September 2003). "Bovine BRCA1 shows classic responses to genotoxic stress but low in vitro transcriptional activation activity". Oncogene 22 (38): 6032–44. doi:10.1038/sj.onc.1206515. PMID 12955082.
  191. ↑ Liu Y, Virshup DM, White RL, Hsu LC (November 2002). "Regulation of BRCA1 phosphorylation by interaction with protein phosphatase 1alpha". Cancer Res. 62 (22): 6357–61. PMID 12438214.
  192. ↑ Scully R, Chen J, Plug A, Xiao Y, Weaver D, Feunteun J et al. (January 1997). "Association of BRCA1 with Rad51 in mitotic and meiotic cells". Cell 88 (2): 265–75. doi:10.1016/S0092-8674(00)81847-4. PMID 9008167.
  193. ↑ 194.0 194.1 194.2 Yarden RI, Brody LC (April 1999). "BRCA1 interacts with components of the histone deacetylase complex". Proc. Natl. Acad. Sci. U.S.A. 96 (9): 4983–8. doi:10.1073/pnas.96.9.4983. PMC 21803. PMID 10220405.
  194. ↑ Chen GC, Guan LS, Yu JH, Li GC, Choi Kim HR, Wang ZY (June 2001). "Rb-associated protein 46 (RbAp46) inhibits transcriptional transactivation mediated by BRCA1". Biochem. Biophys. Res. Commun. 284 (2): 507–14. doi:10.1006/bbrc.2001.5003. PMID 11394910.
  195. ↑ 196.0 196.1 Yarden RI, Brody LC (2001). "Identification of proteins that interact with BRCA1 by Far-Western library screening". J. Cell. Biochem. 83 (4): 521–31. doi:10.1002/jcb.1257. PMID 11746496.
  196. ↑ Li S, Chen PL, Subramanian T, Chinnadurai G, Tomlinson G, Osborne CK et al. (April 1999). "Binding of CtIP to the BRCT repeats of BRCA1 involved in the transcription regulation of p21 is disrupted upon DNA damage". J. Biol. Chem. 274 (16): 11334–8. doi:10.1074/jbc.274.16.11334. PMID 10196224.
  197. ↑ Wong AK, Ormonde PA, Pero R, Chen Y, Lian L, Salada G et al. (November 1998). "Characterization of a carboxy-terminal BRCA1 interacting protein". Oncogene 17 (18): 2279–85. doi:10.1038/sj.onc.1202150. PMID 9811458.
  198. ↑ Li S, Ting NS, Zheng L, Chen PL, Ziv Y, Shiloh Y et al. (July 2000). "Functional link of BRCA1 and ataxia telangiectasia gene product in DNA damage response". Nature 406 (6792): 210–5. doi:10.1038/35018134. PMID 10910365.
  199. ↑ Wu-Baer F, Baer R (November 2001). "Effect of DNA damage on a BRCA1 complex". Nature 414 (6859): 36. doi:10.1038/35102118. PMID 11689934.
  200. ↑ Yu X, Baer R (June 2000). "Nuclear localization and cell cycle-specific expression of CtIP, a protein that associates with the BRCA1 tumor suppressor". J. Biol. Chem. 275 (24): 18541–9. doi:10.1074/jbc.M909494199. PMID 10764811.
  201. ↑ 202.0 202.1 202.2 Fan S, Yuan R, Ma YX, Xiong J, Meng Q, Erdos M et al. (August 2001). "Disruption of BRCA1 LXCXE motif alters BRCA1 functional activity and regulation of RB family but not RB protein binding". Oncogene 20 (35): 4827–41. doi:10.1038/sj.onc.1204666. PMID 11521194.
  202. ↑ Aprelikova ON, Fang BS, Meissner EG, Cotter S, Campbell M, Kuthiala A et al. (October 1999). "BRCA1-associated growth arrest is RB-dependent". Proc. Natl. Acad. Sci. U.S.A. 96 (21): 11866–71. doi:10.1073/pnas.96.21.11866. PMC 18378. PMID 10518542.
  203. ↑ 204.0 204.1 Bochar DA, Wang L, Beniya H, Kinev A, Xue Y, Lane WS et al. (July 2000). "BRCA1 is associated with a human SWI/SNF-related complex: linking chromatin remodeling to breast cancer". Cell 102 (2): 257–65. doi:10.1016/S0092-8674(00)00030-1. PMID 10943845.
  204. ↑ Hill DA, de la Serna IL, Veal TM, Imbalzano AN (April 2004). "BRCA1 interacts with dominant negative SWI/SNF enzymes without affecting homologous recombination or radiation-induced gene activation of p21 or Mdm2". J. Cell. Biochem. 91 (5): 987–98. doi:10.1002/jcb.20003. PMID 15034933.
  205. ↑ Ouchi T, Lee SW, Ouchi M, Aaronson SA, Horvath CM (May 2000). "Collaboration of signal transducer and activator of transcription 1 (STAT1) and BRCA1 in differential regulation of IFN-gamma target genes". Proc. Natl. Acad. Sci. U.S.A. 97 (10): 5208–13. doi:10.1073/pnas.080469697. PMC 25807. PMID 10792030.
  206. ↑ Cable PL, Wilson CA, Calzone FJ, Rauscher FJ, Scully R, Livingston DM et al. (October 2003). "Novel consensus DNA-binding sequence for BRCA1 protein complexes". Mol. Carcinog. 38 (2): 85–96. doi:10.1002/mc.10148. PMID 14502648.
  207. ↑ Zhang H, Wang Q, Kajino K, Greene MI (May 2000). "VCP, a weak ATPase involved in multiple cellular events, interacts physically with BRCA1 in the nucleus of living cells". DNA Cell Biol. 19 (5): 253–63. doi:10.1089/10445490050021168. PMID 10855792.
  208. ↑ Ganesan S, Silver DP, Drapkin R, Greenberg R, Feunteun J, Livingston DM (January 2004). "Association of BRCA1 with the inactive X chromosome and XIST RNA". Philos. Trans. R. Soc. Lond., B, Biol. Sci. 359 (1441): 123–8. doi:10.1098/rstb.2003.1371. PMC 1693294. PMID 15065664.
  209. ↑ Ganesan S, Silver DP, Greenberg RA, Avni D, Drapkin R, Miron A et al. (November 2002). "BRCA1 supports XIST RNA concentration on the inactive X chromosome". Cell 111 (3): 393–405. doi:10.1016/S0092-8674(02)01052-8. PMID 12419249.
  210. ↑ Zheng L, Pan H, Li S, Flesken-Nikitin A, Chen PL, Boyer TG et al. (October 2000). "Sequence-specific transcriptional corepressor function for BRCA1 through a novel zinc finger protein, ZBRK1". Mol. Cell 6 (4): 757–68. doi:10.1016/S1097-2765(00)00075-7. PMID 11090615.

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