関: DNA endonuclease、DNase I

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the 9th letter of the Roman alphabet (同)i

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iodineの化学記号

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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2016/01/20 00:55:32」(JST)

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Deoxyribonuclease I (usually called DNase I), is an endonuclease coded by the human gene DNASE1.^[1] 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.^[2]

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.^[3]^[4] 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.^[5] Alternate transcriptional splice variants of this gene have been observed but have not been thoroughly characterized.^[1]

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 ^[6]

DNase I Sequence Specificity

It has been recently reported that DNase I shows some levels of sequence specificity that may depend on experimental conditions.^[7] 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

^ ^a ^b "Entrez Gene: DNASE1 deoxyribonuclease I".
^ Samejima1, K and 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.
^ 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.
^ 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.
^ 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: 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. doi:10.1371/journal.pone.0069853.

External links

deoxyribonuclease I at the US National Library of Medicine Medical Subject Headings (MeSH)

UpToDate Contents

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English Journal

Five non-synonymous SNPs in the gene encoding human deoxyribonuclease I-like 2 implicated in terminal differentiation of keratinocytes reduce or abolish its activity.

Ueki M, Fujihara J, Kimura-Kataoka K, Takeshita H, Iida R, Yasuda T.SourceDivision of Medical Genetics and Biochemistry, Faculty of Medical Sciences, University of Fukui, Eiheiji, Fukui, Japan.
Electrophoresis.Electrophoresis.2013 Feb;34(3):456-62. doi: 10.1002/elps.201200415. Epub 2013 Jan 3.
Several non-synonymous SNPs in the human deoxyribonuclease I-like 2 (DNase 1L2) gene responsible for DNA degradation during terminal differentiation of epidermal keratinocytes have been identified. However, only limited population data are available, and furthermore the effect of these SNPs on the D
PMID 23161465

Genomic occupancy of HLH, AP1 and Runx2 motifs within a nuclease sensitive site of the Runx2 gene.

Hovhannisyan H, Zhang Y, Hassan MQ, Wu H, Glackin C, Lian JB, Stein JL, Montecino M, Stein GS, van Wijnen AJ.SourceDepartment of Cell Biology, University of Massachusetts Medical School, Worcester, Massachusetts, USA.
Journal of cellular physiology.J Cell Physiol.2013 Feb;228(2):313-21. doi: 10.1002/jcp.22109.
Epigenetic mechanisms mediating expression of the Runt-related transcription factor Runx2 are critical for controlling its osteogenic activity during skeletal development. Here, we characterized bona fide regulatory elements within 120 kbp of the endogenous bone-related Runx2 promoter (P1) in oste
PMID 22886425

Changes in histone modification and DNA methylation of the StAR and Cyp19a1 promoter regions in granulosa cells undergoing luteinization during ovulation in rats.

Lee L, Asada H, Kizuka F, Tamura I, Maekawa R, Taketani T, Sato S, Yamagata Y, Tamura H, Sugino N.SourceDepartment of Obstetrics and Gynecology, Yamaguchi University Graduate School of Medicine, Minamikogushi 1-1-1, Ube 755-8505, Japan.
Endocrinology.Endocrinology.2013 Jan;154(1):458-70. doi: 10.1210/en.2012-1610. Epub 2012 Nov 26.
The ovulatory LH surge induces rapid up-regulation of steroidogenic acute regulatory (StAR) protein and rapid down-regulation of aromatase (Cyp19a1) in granulosa cells (GCs) undergoing luteinization during ovulation. This study investigated in vivo whether epigenetic mechanisms including histone mod
PMID 23183184

Japanese Journal

ノニルフェノールポリエトキシレートはどのようにしてDNA二本鎖切断を誘導するのか

豊岡達士,伊吹裕子
日本毒性学会学術年会 40.1(0), 1002020, 2013
… 本研究ではNPEOsによるDSBs生成メカニズムをDNAのホスホジエステル結合を切断・分解する酵素であるDeoxyribonuclease I (DNase I)に着目し検討、その一端を明らかにしたので報告する。 …
NAID 130004676500

第99回生涯教育講座自己免疫疾患と関連するDeoxyribonuclease Ⅱ(DNase Ⅱ)遺伝子SNPと酵素プロモーター活性の相関解析

竹下治男
島根医学 : the journal of the Shimane Medical Association 32(4), 169-177, 2012-12
NAID 40019567450

Serum deoxyribonuclease l activity can be a useful diagnostic marker for the early diagnosis of unstable angina pectoris or non-ST-segment elevation myocardial infarction

FUJIBAYASHI Kousuke,KAWAI Yasuyuki,KITAYAMA Michihiko,AKAO Hironubu,ISHIDA Ryoko,MOTOYAMA Atsushi,WAKASA Minoru,ARAKAWA Kenichiro,UEKI Misuzu,KAJINAMI Kouji,YASUDA Toshihiro
Journal of cardiology 59(3), 258-265, 2012-05-15
NAID 10031187744

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★リンクテーブル★

リンク元	「DNase I」「デオキシリボヌクレアーゼI」「DNA endonuclease」
拡張検索	「deoxyribonuclease IV」
関連記事	「I」「deoxyribonuclease」「Id」

「DNase I」

Deoxyribonuclease I
Available structures
PDB	Ortholog search: PDBe, RCSB
List of PDB id codes
	4AWN
Identifiers
Symbols	DNASE1 ; DNL1; DRNI
External IDs	OMIM: 125505 MGI: 103157 HomoloGene: 3826 GeneCards: DNASE1 Gene
EC number	3.1.21.1
Gene ontology
Molecular function	• actin binding; • endodeoxyribonuclease activity; • deoxyribonuclease I activity; • protein binding;
Cellular component	• extracellular region; • nucleus; • nuclear envelope; • extracellular exosome;
Biological process	• DNA catabolic process, endonucleolytic; • apoptotic process;
	Sources: Amigo / QuickGO
RNA expression pattern
	More reference expression data
Orthologs
	v; t; e;