Structural and functional properties of CiNTH, an endonuclease III homologue of the ascidian Ciona intestinalis: Critical role of N-terminal region

Seiji Kato, Kazunari Hashiguchi, Kento Igarashi, Takahito Moriwaki, Shin Ichiro Yonekura, Qiu Mei Zhang-Akiyama

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

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 coli, 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. coli 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 β-elimination reaction. Interestingly, the N-terminal 44 amino acids were essential for the DNA glycosylase activity of CiNTH.

Original languageEnglish
Pages (from-to)115-124
Number of pages10
JournalGenes and Genetic Systems
Volume87
Issue number2
DOIs
Publication statusPublished - Jan 1 2012
Externally publishedYes

Keywords

  • Base excision repair
  • Ciona intestinalis
  • Endonuclease III

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics

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