Cloning of a human homolog of the yeast OGG1 gene that is involved in the repair of oxidative DNA damage.
We report the cloning of a human homolog of the yeast OGGC1 gene, which encodes a DNA glycosylase that excises an oxidatively damaged form of guanine, 8-hydroxyguanine (also known as 7,8-dihydro-8-oxoguanine). Since the deduced amino acid sequence (68 amino acids) of a human expressed sequence tag, N55394, matched a short stretch of yeast OGG1 protein with greater than 40% amino acid identity, a full length cDNA clone was isolated from a HeLa cell cDNA library with the N55394 clone as a probe. The cDNA clone encodes a predicted protein of 345 amino acids which is homologous to yeast OGG1 protein throughout the entire polypeptide sequence and shares 38% amino acid identity with yeast OGG1 protein. Moreover, we found that both a human homolog and yeast OGG1 protein possess two distinct DNA binding motifs, a helix-hairpin-helix (HhH) motif and a C2H2 zinc finger like motif, and a domain homologous to human and E. coli MutY proteins. Expression of a human homolog suppressed spontaneous mutagenesis of an E. coli (mutM mutY) mutant as in the case of yeast OGG1 protein. The gene was ubiquitously expressed in a variety of human organs and mapped to chromosome 3p26.2. These results strongly suggest that the gene isolated here is a human counterpart of the yeast OGGI gene and is involved in the repair of oxidative DNA damage in human cells.
Arai
K
K
Biology Division, National Cancer Center Research Institute, Chuo-ku, Tokyo, Japan.
Morishita
K
K
Shinmura
K
K
Kohno
T
T
Kim
S R
SR
Nohmi
T
T
Taniwaki
M
M
Ohwada
S
S
Yokota
J
J
D000595:Amino Acid Sequence; D001483:Base Sequence; D002874:Chromosome Mapping; D003001:Cloning, Molecular; D004249:DNA Damage; D004260:DNA Repair / Q000235:genetics*; D043382:DNA-Formamidopyrimidine Glycosylase; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008969:Molecular Sequence Data; D009699:N-Glycosyl Hydrolases / Q000235:genetics*; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D017386:Sequence Homology, Amino Acid; D012689:Sequence Homology, Nucleic Acid
D009699:N-Glycosyl Hydrolases; D043382:DNA-Formamidopyrimidine Glycosylase