title: Replication-associated repair of adenine:8-oxoguanine mispairs by MYH.
abstract: Cellular DNA is constantly exposed to the risk of oxidation. 8-oxoguanine (8-oxoG) is one of the major DNA lesions generated by oxidation, which is primarily corrected by base excision repair. When it is not repaired prior to replication, replicative DNA polymerases yield misinsertion of an adenine (A) opposite the 8-oxoG on the template strand, generating an A:8-oxoG mispair. MYH, a mammalian homolog of Escherichia coli MutY, is a DNA glycosylase responsible for initiating base excision repair of such a mispair by excising the adenine opposite 8-oxoG. Here, using an in vivo repair system, we show that DNA replication enhances the repair of the A:8-oxoG mispair. Repair efficiency was lower in MYH-deficient murine cells than in MYH-proficient cells. Transfection of the MYH-deficient cells with a wild-type MYH expression vector increased the efficiency of A:8-oxoG repair, indicating that a significant part of this replication-associated repair depends on MYH. Expression of a mutant MYH in which the PCNA binding motif was disrupted did not increase the repair efficiency, thus suggesting that the interaction between PCNA and MYH is critical for MYH-initiated repair of A:8-oxoG.
authors.affiliation: Division of Medical Science, Fox Chase Cancer Center, Philadelphia, PA 19111, USA.
authors.forename: Harutoshi
authors.initials: H
authors.lastname: Hayashi
authors.forename: Yohei
authors.initials: Y
authors.lastname: Tominaga
authors.forename: Seiki
authors.initials: S
authors.lastname: Hirano
authors.forename: Allison E
authors.initials: AE
authors.lastname: McKenna
authors.forename: Yusaku
authors.initials: Y
authors.lastname: Nakabeppu
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Matsumoto
mesh_terms: D000225:Adenine / Q000378:metabolism*; D000818:Animals; D020137:Base Pair Mismatch / Q000235:genetics*; D002460:Cell Line; D045647:DNA Glycosylases; D004260:DNA Repair / Q000235:genetics*; D004261:DNA Replication / Q000235:genetics*; D006147:Guanine / Q000031:analogs & derivatives* / Q000378:metabolism*; D051379:Mice; D008954:Models, Biological; D009154:Mutation; D009699:N-Glycosyl Hydrolases / Q000235:genetics / Q000378:metabolism*; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism
chemical_list: D018809:Proliferating Cell Nuclear Antigen; C024829:8-hydroxyguanine; D006147:Guanine; D045647:DNA Glycosylases; D009699:N-Glycosyl Hydrolases; C061738:mutY adenine glycosylase; D000225:Adenine