Deoxyribonuclease I

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DNASE1
Dnase1.png
Available structures
PDB Ortholog search: PDBe RCSB
Identifiers
Aliases DNASE1, DNL1, DRNI, deoxyribonuclease I
External IDs OMIM: 125505 MGI: 103157 HomoloGene: 3826 GeneCards: 1773
RNA expression pattern
PBB GE DNASE1 210165 at tn.png
More reference expression data
Orthologs
Species Human Mouse
Entrez
Ensembl
UniProt
RefSeq (mRNA)

NM_005223

NM_010061

RefSeq (protein)

NP_005214.2

NP_034191.3

Location (UCSC) Chr 16: 3.61 – 3.68 Mb Chr 16: 4.04 – 4.04 Mb
PubMed search [1] [2]
Wikidata
View/Edit Human View/Edit Mouse

Deoxyribonuclease I (usually called DNase I), is an endonuclease coded by the human gene DNASE1.[3] 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.[4]

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.[5][6] 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.[7] Alternate transcriptional splice variants of this gene have been observed but have not been thoroughly characterized.[3]


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 [8]

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.[9] 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. ^ "Human PubMed Reference:". 
  2. ^ "Mouse PubMed Reference:". 
  3. ^ a b "Entrez Gene: DNASE1 deoxyribonuclease I". 
  4. ^ Samejima, K & 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. 
  5. ^ 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 2906830free to read. PMID 20439745. 
  6. ^ 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. 
  7. ^ 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 55129free to read. PMID 2251263. 
  8. ^ 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. PMC 2669738free to read. PMID 18243105. 
  9. ^ 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. 

Further reading[edit]

External links[edit]