2012年7月13日
Structural and functional properties of CiNTH, an endonuclease III homologue of the ascidian Ciona intestinalis: critical role of N-terminal region
GENES & GENETIC SYSTEMS
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- 巻
- 87
- 号
- 2
- 開始ページ
- 115
- 終了ページ
- 124
- 記述言語
- 英語
- 掲載種別
- 研究論文(学術雑誌)
- DOI
- 10.1266/ggs.87.115
- 出版者・発行元
- GENETICS SOC JAPAN
Oxidatively damaged bases in DNA can cause cell death, mutation and/or cancer induction. To overcome such deleterious effects of DNA base oxidation, cells are equipped with base excision repair (BER) initiated by DNA glycosylases. Endonuclease III (Nth), a major DNA glycosylase, mainly excises oxidatively damaged pyrimidines from DNA. The aims of this study were to obtain an overview of the repair mechanism of oxidatively damaged bases and to elucidate the function of BER in maintaining genome stability during embryogenesis and development. In this study, we used the ascidian Ciona intestinalis because at every developmental stage it is possible to observe the phenotype of individuals with DNA damage or mutations. Sequence alignment analysis revealed that the amino acid sequence of Ciona intestinalis Nth homologue (CiNTH) had high homology with those of Escherichia colt, Saccharomyces cerevisiae, Schizosaccharomyces pombe, Caenorhabditis elegans and human Nth homologues. It was evident that two domains, the Helix-hairpin-Helix and 4Fe-4S cluster domains that are critical regions for the Nth activity, are well conserved in CiNTH. CiNTH efficiently complemented the sensitivity of E. colt nth nei mutant to H2O2. CiNTH was bifunctional, with DNA glycosylase and AP lyase activities. It removed thymine glycol, 5-formyluracil and 8-oxoguanine paired with G from DNA via a beta-elimination reaction. Interestingly, the N-terminal 44 amino acids were essential for the DNA glycosylase activity of CiNTH.
- リンク情報
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- DOI
- https://doi.org/10.1266/ggs.87.115
- J-GLOBAL
- https://jglobal.jst.go.jp/detail?JGLOBAL_ID=201302242562333582
- PubMed
- https://www.ncbi.nlm.nih.gov/pubmed/22820385
- Web of Science
- https://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=JSTA_CEL&SrcApp=J_Gate_JST&DestLinkType=FullRecord&KeyUT=WOS:000308260500006&DestApp=WOS_CPL
- ID情報
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- DOI : 10.1266/ggs.87.115
- ISSN : 1341-7568
- eISSN : 1880-5779
- J-Global ID : 201302242562333582
- PubMed ID : 22820385
- Web of Science ID : WOS:000308260500006