Deoxyribonuclease I

Deoxyribonuclease I (usually called DNase I), is an endonuclease 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
PDBOrtholog search: PDBe RCSB
Identifiers
AliasesDNASE1, DNL1, DRNI, deoxyribonuclease I, deoxyribonuclease 1
External IDsOMIM: 125505 MGI: 103157 HomoloGene: 3826 GeneCards: DNASE1
Gene location (Human)
Chr.Chromosome 16 (human)[1]
Band16p13.3Start3,611,728 bp[1]
End3,680,143 bp[1]
RNA expression pattern
More reference expression data
Orthologs
SpeciesHumanMouse
Entrez

1773

13419

Ensembl

ENSG00000213918

ENSMUSG00000005980

UniProt

P24855

P49183

RefSeq (mRNA)

NM_005223
NM_001351825

NM_010061
NM_001357143

RefSeq (protein)

NP_005214
NP_001338754

NP_034191
NP_001344072

Location (UCSC)Chr 16: 3.61 – 3.68 MbChr 16: 4.04 – 4.04 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/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 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.[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. 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. doi:10.1371/journal.pone.0069853. PMC 3724795. PMID 23922824.

Further reading
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