Abstract
8-Hydroxyguanine (oh8G) is a major base lesion produced by reactive oxygen species. oh8G in DNA causes G:C to T:A transversions and, thus, could be responsible for mutations that lead to carcinogenesis. A human DNA glycosylase/AP lyase encoded by the OGG1 gene has an activity to remove directly oh8G from DNA, and suppresses the mutagenic effect of oh8G. OGG1 protein has a helix-hairpin-helix-GPD motif as a domain for both DNA binding and catalysis, a nuclear localization signal, and a mitochondria targeting signal. Among multiple OGG1 isoforms, OGG1-type la is expressed predominantly in human cells and repairs chromosomal DNA in the nucleus. Inactivation of the OGG1 gene in yeast and mice leads to elevated spontaneous mutation frequency in the cells. The human OGG1 gene maps to chromosome 3p26.2, and allelic deletions of this region occur frequently in a variety of human cancers. Moreover, the OGG1 gene is somatically mutated in some cancer cells and is highly polymorphic among human populations. Repair activities of some mutated and polymorphic OGG1 proteins are lower than those of wild-type OGG1-type la-Ser326 protein and, thus, could be involved in human carcinogenesis.
Publication types
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Comparative Study
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Research Support, Non-U.S. Gov't
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Review
MeSH terms
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Amino Acid Sequence
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Animals
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Carbon-Oxygen Lyases / metabolism
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Cell Transformation, Neoplastic / genetics*
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Cell Transformation, Neoplastic / metabolism
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Chromosomes, Human, Pair 3 / genetics
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Conserved Sequence
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DNA Damage
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DNA Glycosylases*
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DNA Repair / genetics
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DNA Repair / physiology*
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DNA-(Apurinic or Apyrimidinic Site) Lyase
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DNA-Formamidopyrimidine Glycosylase
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Escherichia coli Proteins / physiology
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Exons / genetics
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Genes
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Guanine / analogs & derivatives*
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Guanine / chemistry
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Humans
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Kinetics
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Mice
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Molecular Sequence Data
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Mutagenesis
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N-Glycosyl Hydrolases / genetics
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N-Glycosyl Hydrolases / physiology*
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Neoplasms / genetics
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Oxidation-Reduction
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Oxidative Stress
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Polymorphism, Genetic
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Protein Isoforms / genetics
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Protein Isoforms / physiology
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Rats
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Reactive Oxygen Species / toxicity
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Saccharomyces cerevisiae Proteins / physiology
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Sequence Alignment
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Sequence Homology, Amino Acid
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Species Specificity
Substances
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Escherichia coli Proteins
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Protein Isoforms
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Reactive Oxygen Species
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Saccharomyces cerevisiae Proteins
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8-hydroxyguanine
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Guanine
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DNA Glycosylases
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N-Glycosyl Hydrolases
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mutY adenine glycosylase
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DNA-Formamidopyrimidine Glycosylase
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DNA-formamidopyrimidine glycosylase, E coli
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Carbon-Oxygen Lyases
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DNA-(Apurinic or Apyrimidinic Site) Lyase