Genomic structure and chromosomal localization of the mouse Ogg1 gene that is involved in the repair of 8-hydroxyguanine in DNA damage |
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| Authors: | Masachika Tani Kazuya Shinmura Takashi Kohno Toshihiko Shiroishi Shigeharu Wakana Su-Ryang Kim Takehiko Nohmi Hiroshi Kasai Seiichi Takenoshita Yukio Nagamachi Jun Yokota |
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| Affiliation: | (1) Biology Division, National Cancer Center Research Institute, 1-1, Tsukiji 5-chome, Chuo-ku, Tokyo 104, Japan, JP;(2) First Department of Surgery, Gunma University School of Medicine, 39-22, Showa-machi 3-chome, Maebashi, Gunma 371, Japan, JP;(3) Mammalian Genetics Laboratory, National Institute of Genetics, 1-111, Tanida, Mishima, Shizuoka 411, Japan, JP;(4) Central Institute for Experimental Animals, 1430, Nogawa, Miyamae-ku, Kawasaki, Kanagawa 216, Japan, JP;(5) Division of Genetics and Mutagenesis, National Institute of Health Science, 18-1, 1-chome, Kamiyoga, Setagaya-ku, Tokyo 158, Japan, JP;(6) Department of Environmental Oncology, University of Occupational and Environmental Health, 1-1, Isegaoka, Yahatanishi-ku, Kitakyushu 807, Japan, JP |
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| Abstract: | 8-Hydroxyguanine (7,8-dihydro-8-oxoguanine: oh8Gua) is a damaged form of guanine induced by oxygen-free radicals and causes GC to TA transversions. Previously we isolated the hOGG1 gene, a human homolog of the yeast OGG1 gene, which encodes a DNA glycosylase and lyase to excise oh8Gua in DNA. In this study, we isolated a mouse homolog (Ogg1) of the OGG1 gene, characterized oh8Gua-specific DNA glycosylase/AP lyase activities of its product, and determined chromosomal localization and exon-intron organization of this gene. A predicted protein possessed five domains homologous to human and yeast OGG1 proteins. Helix-hairpin-helix and C2H2 zinc finger-like DNA-binding motifs found in human and yeast OGG1 proteins were also retained in mouse Ogg1 protein. The properties of a GST fusion protein were identical to human and yeast OGG1 proteins in glycosylase/lyase activities, their substrate specificities, and suppressive activities against the spontaneous mutagenesis of an Escherichia coli mutM mutY double mutant. The mouse Ogg1 gene was mapped to Chromosome (Chr) 6, and consisted of 7 exons approximately 6 kb long. Two DNA-binding motifs were encoded in exons 4 through 5. These data will facilitate the investigation of the OGG1 gene to elucidate the relationship between oxidative DNA damage and carcinogenesis. Received: 17 July 1997 / Accepted: 15 September 1997 |
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