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Deoxyribonuclease I

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(Redirected from DNase I) Protein-coding gene in the species Homo sapiens
DNASE1
Available structures
PDBOrtholog search: PDBe RCSB
List of PDB id codes

4AWN

Identifiers
AliasesDNASE1, DNL1, DRNI, deoxyribonuclease I, deoxyribonuclease 1
External IDsOMIM: 125505; MGI: 103157; HomoloGene: 3826; GeneCards: DNASE1; OMA:DNASE1 - orthologs
Gene location (Human)
Chromosome 16 (human)
Chr.Chromosome 16 (human)
Chromosome 16 (human)Genomic location for DNASE1Genomic location for DNASE1
Band16p13.3Start3,611,728 bp
End3,680,143 bp
Gene location (Mouse)
Chromosome 16 (mouse)
Chr.Chromosome 16 (mouse)
Chromosome 16 (mouse)Genomic location for DNASE1Genomic location for DNASE1
Band16 A1|16 2.37 cMStart3,854,806 bp
End3,857,888 bp
RNA expression pattern
Bgee
HumanMouse (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
Cellular component
Biological process
Sources:Amigo / QuickGO
Orthologs
SpeciesHumanMouse
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 MbChr 16: 3.85 – 3.86 Mb
PubMed search
Wikidata
View/Edit HumanView/Edit Mouse

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

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. 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. Alternate transcriptional splice variants of this gene have been observed but have not been thoroughly characterized.


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

DNase I Sequence Specificity

It has been recently reported that DNase I shows some levels of sequence specificity that may depend on experimental conditions. 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: ENSG00000213918Ensembl, May 2017
  2. ^ GRCm38: Ensembl release 89: ENSMUSG00000005980Ensembl, 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

External links

Hydrolase: esterases (EC 3.1)
3.1.1: Carboxylic
ester hydrolases
3.1.2: Thioesterase
3.1.3: Phosphatase
3.1.4:
Phosphodiesterase
3.1.6: Sulfatase
Nuclease (includes
deoxyribonuclease
and ribonuclease)
3.1.11-16:
Exonuclease
Exodeoxyribonuclease
Exoribonuclease
3.1.21-31:
Endonuclease
Endodeoxyribonuclease
Endoribonuclease
either deoxy- or ribo-    
Enzymes
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Regulation
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