Deoxyribonuclease I
| Deoxyribonuclease I | |||||||||||||
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| Identifiers | |||||||||||||
| Symbols | DNASE1; DNL1; DRNI | ||||||||||||
| External IDs | OMIM: 125505 MGI: 103157 HomoloGene: 3826 GeneCards: DNASE1 Gene | ||||||||||||
| EC number | 3.1.21.1 | ||||||||||||
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| RNA expression pattern | |||||||||||||
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| Orthologs | |||||||||||||
| Species | Human | Mouse | |||||||||||
| Entrez | 1773 | 13419 | |||||||||||
| Ensembl | ENSG00000213918 | ENSMUSG00000005980 | |||||||||||
| UniProt | P24855 | P49183 | |||||||||||
| RefSeq (mRNA) | NM_005223 | NM_010061 | |||||||||||
| RefSeq (protein) | NP_005214 | NP_034191 | |||||||||||
| Location (UCSC) | Chr 16: 3.66 – 3.73 Mb | Chr 16: 4.04 – 4.04 Mb | |||||||||||
| PubMed search | |||||||||||||
Deoxyribonuclease I (usually called DNase I), is an endonuclease coded by the human gene DNASE1.[1] DNase I is a nuclease that cleaves DNA preferentially at phosphodiester linkages adjacent to a pyrimidine nucleotide, yielding 5'-phosphate-terminated polynucleotides with a free hydroxyl group on position 3', on average producing tetranucleotides. It acts on single-stranded DNA, double-stranded DNA, and chromatin. In addition to its role as a waste-management endonuclease, it has been suggested to be one of the deoxyribonucleases responsible for DNA fragmentation during apoptosis.[2]
DNase I binds to the cytoskeletal protein actin. It binds actin monomers with very high (sub-nanomolar) affinity and actin polymers with lower affinity. The function of this interaction is unclear. However, since actin-bound DNase I is enzymatically inactive, the DNase-actin complex might be a storage form of DNase I that prevents damage of the genetic information.
This gene encodes a member of the DNase family. This protein is stored in the zymogen granules of the nuclear envelope and functions by cleaving DNA in an endonucleolytic manner. At least six autosomal codominant alleles have been characterized, DNASE1*1 through DNASE1*6, and the sequence of DNASE1*2 represented in this record. Mutations in this gene, as well as factor inactivating its enzyme product, have been associated with systemic lupus erythematosus (SLE), an autoimmune disease.[3][4] A recombinant form of this protein is used to treat one of the symptoms of cystic fibrosis by hydrolyzing the extracellular DNA in sputum and reducing its viscosity.[5] Alternate transcriptional splice variants of this gene have been observed but have not been thoroughly characterized.[1]
In genomics
In genomics, DNase I hypersensitive sites are thought to be characterized by open, accessible chromatin; therefore, a DNase I sensitivity assay is a widely used methodology in genomics for identifying which regions of the genome are likely to contain genes [6]
References
- ↑ 1.0 1.1 "Entrez Gene: DNASE1 deoxyribonuclease I".
- ↑ Samejima1, K and Earnshaw, W.C. (2005). "Trashing the genome: the role of nucleases during apoptosis". Nat Rev Mol Cell Biol 6: 677–88. doi:10.1038/nrm1715.
- ↑ Hakkim A, Fürnrohr BG, Amann K, Laube B, Abed UA, Brinkmann V, Herrmann M, Voll RE, Zychlinsky A. (2010). "Impairment of neutrophil extracellular trap degradation is associated with lupus nephritis". Proc Natl Acad Sci U S A 107 (21): 9813–8. doi:10.1073/pnas.0909927107. PMC 2906830. PMID 20439745.
- ↑ Yasutomo K, Horiuchi T, Kagami S, et al. (2001). "Mutation of DNASE1 in people with systemic lupus erythematosus". Nat. Genet. 28 (4): 313–4. doi:10.1038/91070. PMID 11479590.
- ↑ Shak S, Capon DJ, Hellmiss R, et al. (1991). "Recombinant human DNase I reduces the viscosity of cystic fibrosis sputum". Proc. Natl. Acad. Sci. U.S.A. 87 (23): 9188–92. doi:10.1073/pnas.87.23.9188. PMC 55129. PMID 2251263.
- ↑ Boyle AP, Davis S, Shulha HP, Meltzer P, Margulies EH, Weng Z, Furey TS, Crawford GE (2008). "High-resolution mapping and characterization of open chromatin across the genome". Cell 132: 311–322. doi:10.1016/j.cell.2007.12.014.
Further reading
- Lachmann PJ (2003). "Lupus and desoxyribonuclease". Lupus 12 (3): 202–6. doi:10.1191/0961203303lu357xx. PMID 12708782.
- Yasuda T, Awazu S, Sato W, et al. (1991). "Human genetically polymorphic deoxyribonuclease: purification, characterization, and multiplicity of urine deoxyribonuclease I". J. Biochem. 108 (3): 393–8. PMID 2277032.
- Kishi K, Yasuda T, Ikehara Y, et al. (1990). "Human serum deoxyribonuclease I (DNase I) polymorphism: pattern similarities among isozymes from serum, urine, kidney, liver, and pancreas". Am. J. Hum. Genet. 47 (1): 121–6. PMC 1683738. PMID 2349940.
- Kabsch W, Mannherz HG, Suck D, et al. (1990). "Atomic structure of the actin:DNase I complex". Nature 347 (6288): 37–44. doi:10.1038/347037a0. PMID 2395459.
- Kishi K, Yasuda T, Awazu S, Mizuta K (1989). "Genetic polymorphism of human urine deoxyribonuclease I". Hum. Genet. 81 (3): 295–7. doi:10.1007/BF00279009. PMID 2921043.
- Rosenstreich DL, Tu JH, Kinkade PR, et al. (1988). "A human urine-derived interleukin 1 inhibitor. Homology with deoxyribonuclease I". J. Exp. Med. 168 (5): 1767–79. doi:10.1084/jem.168.5.1767. PMC 2189114. PMID 3263467.
- Yasuda T, Nadano D, Takeshita H, et al. (1995). "Molecular analysis of the third allele of human deoxyribonuclease I polymorphism". Ann. Hum. Genet. 59 (Pt 2): 139–47. doi:10.1111/j.1469-1809.1995.tb00737.x. PMID 7625762.
- Yasuda T, Kishi K, Yanagawa Y, Yoshida A (1995). "Structure of the human deoxyribonuclease I (DNase I) gene: identification of the nucleotide substitution that generates its classical genetic polymorphism". Ann. Hum. Genet. 59 (Pt 1): 1–15. doi:10.1111/j.1469-1809.1995.tb01601.x. PMID 7762978.
- Yasuda T, Nadano D, Iida R, et al. (1995). "Chromosomal assignment of the human deoxyribonuclease I gene, DNASE 1 (DNL1), to band 16p13.3 using the polymerase chain reaction". Cytogenet. Cell Genet. 70 (3–4): 221–3. doi:10.1159/000134038. PMID 7789176.
- Yasuda T, Nadano D, Takeshita H, et al. (1995). "The molecular basis for genetic polymorphism of human deoxyribonuclease I: identification of the nucleotide substitution that generates the fourth allele". FEBS Lett. 359 (2–3): 211–4. doi:10.1016/0014-5793(95)00037-A. PMID 7867802.
- Yasuda T, Nadano D, Tenjo E, et al. (1996). "Genotyping of human deoxyribonuclease I polymorphism by the polymerase chain reaction". Electrophoresis 16 (10): 1889–93. doi:10.1002/elps.11501601310. PMID 8586059.
- Iida R, Yasuda T, Takeshita H, et al. (1996). "Identification of the nucleotide substitution that generates the fourth polymorphic site in human deoxyribonuclease I (DNase I)". Hum. Genet. 98 (4): 415–8. doi:10.1007/s004390050231. PMID 8792814.
- Iida R, Yasuda T, Aoyama M, et al. (1998). "The fifth allele of the human deoxyribonuclease I (DNase I) polymorphism". Electrophoresis 18 (11): 1936–9. doi:10.1002/elps.1150181108. PMID 9420147.
- Yasuda T, Takeshita H, Iida R, et al. (1999). "A new allele, DNASE1*6, of human deoxyribonuclease I polymorphism encodes an Arg to Cys substitution responsible for its instability". Biochem. Biophys. Res. Commun. 260 (1): 280–3. doi:10.1006/bbrc.1999.0900. PMID 10381379.
- Oliveri M, Daga A, Cantoni C, et al. (2001). "DNase I mediates internucleosomal DNA degradation in human cells undergoing drug-induced apoptosis". Eur. J. Immunol. 31 (3): 743–51. doi:10.1002/1521-4141(200103)31:3<743::AID-IMMU743>3.0.CO;2-9. PMID 11241278.
- Otterbein LR, Graceffa P, Dominguez R (2001). "The crystal structure of uncomplexed actin in the ADP state". Science 293 (5530): 708–11. doi:10.1126/science.1059700. PMID 11474115.
- Yasutomo K, Horiuchi T, Kagami S, et al. (2001). "Mutation of DNASE1 in people with systemic lupus erythematosus". Nat. Genet. 28 (4): 313–4. doi:10.1038/91070. PMID 11479590.
- Ballweber E, Galla M, Aktories K, et al. (2001). "Interaction of ADP-ribosylated actin with actin binding proteins". FEBS Lett. 508 (1): 131–5. doi:10.1016/S0014-5793(01)03040-X. PMID 11707283.
- Tsutsumi S, Kaneko Y, Asao T, et al. (2002). "DNase I is present in the chief cells of human and rat stomachs". Histochem. J. 33 (9–10): 531–5. doi:10.1023/A:1014999624430. PMID 12005024.
External links
- deoxyribonuclease I at the US National Library of Medicine Medical Subject Headings (MeSH)
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