Nibrin

From Wikipedia, the free encyclopedia

Nibrin

Identifiers

NBN; AT-V1; AT-V2; ATV; FLJ10155; MGC87362; NBS; NBS1

External IDs

OMIM: 602667 MGI: 1351625 HomoloGene: 1858

Gene ontology
Molecular Function:	• damaged DNA binding • transcription factor binding • protein N-terminus binding
Cellular Component:	• chromosome, telomeric region • intracellular • nucleus • replication fork • chromosome • Mre11 complex • nuclear inclusion body
Biological Process:	• DNA damage checkpoint • telomere maintenance • double-strand break repair • cell cycle • cell cycle arrest • mitotic cell cycle G2/M transition DNA damage checkpoint • meiosis • cell proliferation • regulation of DNA replication initiation • DNA damage response, signal transduction by p53 class mediator • G1/S transition checkpoint • regulation of balance

RNA expression pattern

More reference expression data

Orthologs

Human

Mouse

Refseq

NM_001024688 (mRNA)
NP_001019859 (protein)

NM_013752 (mRNA)
NP_038780 (protein)

Location

Chr 8: 91.01 - 91.07 Mb

Chr 4: 15.89 - 15.92 Mb

Pubmed search

[1]

[2]

1 Nibrin
2 Cellular Response to DSBs
3 Double Strand Breaks (DSBs)
4 DSB Mutations
5 References
6 Further reading
7 External links

[edit] Nibrin

Nibrin is a protein associated with the repair of double stran breaks(DSBs) which pose serious damage to a genome. It is a 754 amino acid protein identified as a member of the NBS1/hMre11/RAD50(N/M/R, more commonly referred to as MRN) double strand DNA break repair complex.^[1] This complex recognizes DNA damage and rapidly relocates to DSB sites and forms nuclear foci. It also has a role in regulation of N/M/R (MRN) protein complex activity which includes end-processing of both physiological and mutagenic DNA double strand breaks (DSBs).^[2]

[edit] Cellular Response to DSBs

Cellular response is performed by damage sensors, effectors of lesion repair and signal transduction. The central role is carried out by ataxia-telangiectasia mutated(ATM) by activating the DSB signaling cascade, phosphorylating downstream substrates such as histone H2AX and NBS1. NBS1 relocates to DSB sites by interaction of FHA/BRCT domains wih phosphorylated histone H2AX. Once it interacts with nibrin c-terminal hMre11-binding domain, hMre11 and hRAD50 relocate from the cytoplasm to the nucleus then to sites of DSBs. They finally relocate to N/M/R where they form the foci at the site of damage.^[3]

[edit] Double Strand Breaks (DSBs)

DSBs occur during V(D)J recombination during early B and T cell development. This is at the point when the cells of the immune system are developing and the DSBs effect the development of lymphoid cells. DSBs also occur in immunoglobulin class switch in mature B cells.^[2] More frequently, however, DSBs are caused by mutagenic agents like radiomimetic chemicals and ionizing radiation(IR).

[edit] DSB Mutations

As mentioned, DSBs cause extreme damage to DNA. One such mutation is associated with Nijmegen breakage syndrome (NBS), a radiation hyper-sensitive disease.^[4] It is a rare inherited autosomal recessive condition of chrosomal instability. It has been linked to mutations within exons 6-10 in the NBS1 gene which results in a truncated protein.^[2] Characteristics of NBS include microcephaly, cranial characteristics, growth retardation, impaired sexual maturation, immunodeficiency/recurring infections and a predisposition to cancer. This predisposition to cancer may be linked to the DSBs occurring at the development of lymphoid cells.

[edit] References

^ Atlas of Genetics and Cytogenetics in Oncology and Haematology - NBS1. Retrieved on 2008-02-12.
^ ^a ^b ^c eMedicine - Nijmegen Breakage Syndrome. Retrieved on 2008-02-12.
^ Molecular Biology
^ Kobayashi J (2004). "Molecular mechanism of the recruitment of NBS1/hMRE11/hRAD50 complex to DNA double-strand breaks: NBS1 binds to gamma-H2AX through FHA/BRCT domain". J. Radiat. Res. 45 (4): 473–8. PMID 15635255.

[edit] Further reading

Kobayashi J, Antoccia A, Tauchi H, et al. (2005). "NBS1 and its functional role in the DNA damage response.". DNA Repair (Amst.) 3 (8-9): 855–61. doi:10.1016/j.dnarep.2004.03.023. PMID 15279770.
Digweed M, Sperling K (2005). "Nijmegen breakage syndrome: clinical manifestation of defective response to DNA double-strand breaks.". DNA Repair (Amst.) 3 (8-9): 1207–17. doi:10.1016/j.dnarep.2004.03.004. PMID 15279809.
Matsuura S, Kobayashi J, Tauchi H, Komatsu K (2004). "Nijmegen breakage syndrome and DNA double strand break repair by NBS1 complex.". Adv. Biophys. 38: 65–80. PMID 15493328.
Zhang Y, Zhou J, Lim CU (2006). "The role of NBS1 in DNA double strand break repair, telomere stability, and cell cycle checkpoint control.". Cell Res. 16 (1): 45–54. doi:10.1038/sj.cr.7310007. PMID 16467875.