Cloning and characterization of mammalian 8-hydroxyguanine-specific DNA glycosylase/apurinic, apyrimidinic lyase, a functional mutM homologue

Hiroyuki Aburatani, Yoshitaka Hippo, Toshimitsu Ishida, Rieko Takashima, Chikako Matsuba, Tatsuhiko Kodama, Masashi Takao, Akira Yasui, Kazuo Yamamoto, Midori Asano, Kazuhiro Fukasawa, Tomoko Yoshinari, Hideo Inoue, Eiko Ohtsuka, Susumu Nishimura

研究成果: Article査読

315 被引用数 (Scopus)

抄録

8-Hydroxyguanine (8-OH-G) is one of the major DNA oxidation products implicated in mutagenesis induced by oxygen radical-forming agents, including ionizing radiation. It is also believed to be involved in spontaneous mutation induced by metabolically produced oxygen radicals. A mammalian homologue of 8-OH-G glycosylase/apurinic, apyrimidinic lyase (mutM homologue, MMH) has been identified in the EST database (for expressed sequence tags) through a homology search with yeast OGG1 protein. The human MMH protein (hMMH), 34% identical to the yeast OGG1 protein, is a member of the DNA repair protein superfamily. The hMMH gene was composed of seven exons, with the alternate last exon, exon 8, producing three major alternative splicing isoforms, because splicing of the sixth intron was optional. The hMMH protein expressed in Escherichia coli revealed the glycosylase activity and apurinic, apyrimidixic lyase activity on duplex DNA containing 8-OH-G. The hMMH protein can rescue a spontaneous mutator strain of E. coli lacking mutM and mutY. By the introduction of recombinant hMMH, the rate of mutation, the formation of rifampicin-resistant revertants, was reduced by 4-7 fold. Genomic structure analysis showed that 3' exons of the hMMH gene are transcribed on the antisense strand of the calcium-dependent calmodulin kinase 1 gene.

本文言語English
ページ(範囲)2151-2156
ページ数6
ジャーナルCancer Research
57
11
出版ステータスPublished - 1997 6 1

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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