Deoxyribonuclease I
| DNASE1 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Aliases | DNASE1, DNL1, DRNI, deoxyribonuclease I, deoxyribonuclease 1 | |||||||||||||||||||||||||||||||||||||||||||||||||||||
| External IDs | OMIM: 125505; MGI: 103157; GeneCards: DNASE1 | |||||||||||||||||||||||||||||||||||||||||||||||||||||
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Deoxyribonuclease I (usually called DNase I), is an enzyme that in humans is encoded by the gene DNASE1.[5] As its name suggests, DNase I functions as a DNase, which means it is involved in cleaving and breaking down DNA.[5] This type of DNase is found in blood and secreted into various types of bodily fluid.[6] A recombinant form of this enzyme, called dornase alfa, is used in the treatment of cystic fibrosis by making the DNA-filled mucus less viscous.[7]
DNase I is an endonuclease of the DNase family 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.[8]
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 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 of the gene DNASE 1 have been characterized, DNASE1*1 through DNASE1*6, with 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.[9][10] 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.[11] Alternate transcriptional splice variants of this gene have been observed but have not been thoroughly characterized.[5]
In genomics
[edit]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 active genes [12]
DNase I Sequence Specificity
[edit]It has been recently reported that DNase I shows some levels of sequence specificity that may depend on experimental conditions.[13] In contrast to other enzymes which have high substrate specificity, DNase I certainly does not cleave with an absolute sequence specificity. However, cleavage at sites that contain C or G at their 3' end is less efficient.
References
[edit]- 1 2 3 GRCh38: Ensembl release 89: ENSG00000213918 – Ensembl, May 2017
- 1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000005980 – Ensembl, May 2017
- ↑ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ↑ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- 1 2 3 "Entrez Gene: DNASE1 deoxyribonuclease I".
- ↑ "P24855 · DNAS1_HUMAN". uniprot.org. UniProt consortium. Retrieved 2026-09-01.
- ↑ Pulmozyme (dornase alfa) inhalation solution: US Prescribing Information (FDA label, revised February 2024) (PDF) (Report). U.S. Food and Drug Administration. Retrieved 2025-12-24.
- ↑ Samejima, K. & Earnshaw, W.C. (2005). "Trashing the genome: the role of nucleases during apoptosis". Nat Rev Mol Cell Biol. 6 (9): 677–88. doi:10.1038/nrm1715. PMID 16103871. S2CID 13948545.
- ↑ 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. Bibcode:2010PNAS..107.9813H. 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. S2CID 21277651.
- ↑ 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 (2): 311–322. doi:10.1016/j.cell.2007.12.014. PMC 2669738. PMID 18243105.
- ↑ Koohy, Hashem; Down, Thomas A.; Hubbard, Tim J.; Mariño-Ramírez, Leonardo (26 July 2013). "Chromatin Accessibility Data Sets Show Bias Due to Sequence Specificity of the DNase I Enzyme". PLOS ONE. 8 (7) e69853. Bibcode:2013PLoSO...869853K. doi:10.1371/journal.pone.0069853. PMC 3724795. PMID 23922824.
Further reading
[edit]- Lachmann PJ (2003). "Lupus and desoxyribonuclease". Lupus. 12 (3): 202–6. doi:10.1191/0961203303lu357xx. PMID 12708782. S2CID 43058677.
- 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. doi:10.1093/oxfordjournals.jbchem.a123212. 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. Bibcode:1990Natur.347...37K. doi:10.1038/347037a0. PMID 2395459. S2CID 925337.
- 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. S2CID 20420713.
- 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. S2CID 43729378.
- 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. S2CID 23914004.
- 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. Bibcode:1995FEBSL.359..211Y. doi:10.1016/0014-5793(95)00037-A. PMID 7867802. S2CID 21461181.
- 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. S2CID 35528773.
- 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. S2CID 6393565.
- 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. S2CID 8969865.
- 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. Bibcode:1999BBRC..260..280Y. 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. S2CID 32330090.
- 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. S2CID 12030018.
- 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. S2CID 21277651.
- Ballweber E, Galla M, Aktories K, et al. (2001). "Interaction of ADP-ribosylated actin with actin binding proteins". FEBS Lett. 508 (1): 131–5. Bibcode:2001FEBSL.508..131B. doi:10.1016/S0014-5793(01)03040-X. PMID 11707283. S2CID 7241702.
- 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. S2CID 10324827.
External links
[edit]- deoxyribonuclease+I at the U.S. National Library of Medicine Medical Subject Headings (MeSH)
