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. 1992 Aug 1;89(15):7022–7025. doi: 10.1073/pnas.89.15.7022

Evidence that MutY and MutM combine to prevent mutations by an oxidatively damaged form of guanine in DNA.

M L Michaels 1, C Cruz 1, A P Grollman 1, J H Miller 1
PMCID: PMC49637  PMID: 1495996

Abstract

It has been previously shown both in vivo and in vitro that DNA synthesis past an oxidatively damaged form of guanine, 7,8-dihydro-8-oxoguanine (8-oxoG), can result in the misincorporation of adenine (A) opposite the 8-oxodG. In this study we show that MutY glycosylase is active on a site-specific, oxidatively damaged A/8-oxoG mispair and that it removes the undamaged adenine from this mispair. Strains that lack active MutY protein have elevated rates of G.C----T.A transversions. We find that the mutator phenotype of a mutY strain can be fully complemented by overexpressing MutM protein (Fpg protein) from a plasmid clone. The MutM protein removes 8-oxoG lesions from DNA. In addition, we have isolated a strain with a chromosomal mutation that suppresses the mutY phenotype and found that this suppressor also overexpresses MutM. Finally, a mutY mutM double mutant has a 25- to 75-fold higher mutation rate than either mutator alone. The data strongly suggest that MutY is part of an intricate repair system directed against 8-oxoG lesions in nucleic acids and that the primary function of MutY in vivo is the removal of adenines that are misincorporated opposite 8-oxoG lesions during DNA synthesis.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

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