Substitution of Ala for Tyr567 in RB69 DNA polymerase allows dAMP and dGMP to be inserted opposite Guanidinohydantoin .

ABSTRACT: Continuous oxidative damage inflicted on DNA produces 7,8-dihydro-8-oxoguanine (8-oxoG), a commonly occurring lesion that can potentially cause cancer by producing G → T transversions during DNA replication. Mild oxidation of 8-oxoG leads to the formation of hydantoins, specifically guanidinohydantoin (Gh) and spiroiminodihydantoin (Sp), which are 100% mutagenic because they encode almost exclusively the insertion of dAMP and dGMP (encoding G → T and G → C transversions, respectively). The wild-type (wt) pol α family DNA polymerase from bacteriophage RB69 (RB69pol) inserts dAMP and dGMP with low efficiency when situated opposite Gh. In contrast, the RB69pol Y567A mutant inserts both of these dNMPs opposite Gh with >100-fold higher efficiency than wt. We now report the crystal structure of

SUBMITTER: Beckman J 

PROVIDER: S-EPMC3755731 | biostudies-literature | 2010 Oct

REPOSITORIES: biostudies-literature