Deoxyribonuclease I

Deoxyribonuclease I (usually called DNase I), is an endonuclease of the DNase family coded by the human gene DNASE1.^[5] 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.^[6]

DNASE1
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 4AWN
Identifiers
Aliases	DNASE1, DNL1, DRNI, deoxyribonuclease I, deoxyribonuclease 1
External IDs	OMIM: 125505; MGI: 103157; HomoloGene: 3826; GeneCards: DNASE1; OMA:DNASE1 - orthologs
Gene location (Human) Chr. Chromosome 16 (human)[1] Band 16p13.3 Start 3,611,728 bp[1] End 3,680,143 bp[1]
Gene location (Mouse) Chr. Chromosome 16 (mouse)[2] Band 16 A1|16 2.37 cM Start 3,854,806 bp[2] End 3,857,888 bp[2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in duodenum jejunal mucosa tendon of biceps brachii body of pancreas buccal mucosa cell mucosa of ileum anterior pituitary body of stomach granulocyte right hemisphere of cerebellum Top expressed in parotid gland lacrimal gland submandibular gland right kidney vestibular membrane of cochlear duct human kidney stria vascularis jejunum proximal tubule vestibular sensory epithelium More reference expression data BioGPS More reference expression data
Gene ontology Molecular function nuclease activity endonuclease activity deoxyribonuclease I activity actin binding protein binding hydrolase activity deoxyribonuclease activity DNA binding Cellular component extracellular region extracellular exosome nuclear envelope nucleus Biological process DNA catabolic process nucleic acid phosphodiester bond hydrolysis apoptotic process DNA catabolic process, endonucleolytic neutrophil activation involved in immune response regulation of acute inflammatory response regulation of neutrophil mediated cytotoxicity Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 1773 13419 Ensembl ENSG00000213918 ENSMUSG00000005980 UniProt P24855 P49183 RefSeq (mRNA) NM_005223 NM_001351825 NM_001387135 NM_001387139 NM_001387140 NM_001387141 NM_010061 NM_001357143 RefSeq (protein) NP_005214 NP_001338754 NP_034191 NP_001344072 Location (UCSC) Chr 16: 3.61 – 3.68 Mb Chr 16: 3.85 – 3.86 Mb PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

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, 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.^[7][8] 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.^[9] Alternate transcriptional splice variants of this gene have been observed but have not been thoroughly characterized.^[5]

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 active genes ^[10]

DNase I Sequence Specificity

It has been recently reported that DNase I shows some levels of sequence specificity that may depend on experimental conditions.^[11] 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

1. GRCh38: Ensembl release 89: ENSG00000213918 – Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000005980 – Ensembl, May 2017
3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
5. "Entrez Gene: DNASE1 deoxyribonuclease I".
6. 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.
7. 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.
8. 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.
9. 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.
10. 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.
11. 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

• 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. 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. 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. 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

• deoxyribonuclease+I at the U.S. National Library of Medicine Medical Subject Headings (MeSH)