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

Research output: Contribution to journalArticlepeer-review

315 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)2151-2156
Number of pages6
JournalCancer Research
Volume57
Issue number11
Publication statusPublished - 1997 Jun 1

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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