Disease relevance of OGG1

• No significant acceleration was observed in the repair of either a single AP site cleaved by the bifunctional glycosylase NTH of E. coli or the repair of a single 8-oxoguanine, initiated by the bifunctional glycosylase OGG1 [1].

High impact information on OGG1

• In S. cerevisiae, mutations in MSH2 or MSH6 caused a synergistic increase in mutation rate in combination with mutations in OGG1, which encodes a MutM homolog, resulting in a 140- to 218-fold increase in the G:C-to-T:A transversion rate [2].
• Eukaryotic cells use a specific DNA glycosylase, the product of the OGG1 gene, to excise 8-oxoG from DNA [3].
• DNA sequencing identified an open reading frame, designated OGG1, which encodes a protein of 376 amino acids with a molecular mass of 43 kDa [4].
• The OGG1 gene was inserted in plasmid pUC19, yielding pYSB110 [4].
• A search of the yeast genome database using peptide sequences from the protein identified a gene, OGG1, encoding a predicted 43 kDa (376 amino acid) protein, identical to one identified independently by complementation cloning [5].

Biological context of OGG1

• Role of OGG1 and NTG2 in the repair of oxidative DNA damage and mutagenesis induced by hydrogen peroxide in Saccharomyces cerevisiae: relationships with transition metals iron and copper [6].
• Cloning of the OGG1 gene from Saccharomyces cerevisiae has revealed that DNA glycosylases are not necessarily conserved throughout phylogeny, yet there is a DNA-repair protein superfamily with a wide substrate specificity found from bacteria to man [7].
• The biological relevance of oxidative DNA damage has been unveiled by the identification of genes such as fpg of E. coli or OGG1 of Saccharomyces cerevisiae [8].
• We report here the cloning, by sequence homology to the yeast OGG1, of a mouse cDNA coding for a 8-OH-Gua DNA glycosylase with 84% and 38% identity to the human and yeast relevant proteins, respectively [9].
• The disruption of the OGG1 gene does not compromise the viability of haploid cells, therefore it is not an essential gene [10].

Associations of OGG1 with chemical compounds

• Excision of 8-oxoguanine within clustered damage by the yeast OGG1 protein [11].
• The ability of yeast OGG1 to excise 8-oxoG was determined when another type of damage [dihydrothymine, uracil, 8-oxoG, abasic (AP) site or various types of single-strand breaks (SSBs)] is present on the complementary strand 1, 3 or 5 bases 5' or 3' opposite to 8-oxoG [11].

Other interactions of OGG1

• The roles of OGG1 and NTG2 genes in the repair of lethal and mutagenic oxidative lesions induced by H2O2 and their relationships with iron and copper ions are discussed [6].

Analytical, diagnostic and therapeutic context of OGG1

• Mutations of K241 to Gln (K241Q) and Arg (K241R) have been obtained after site directed mutagenesis of OGG1 [12].

References