ANTIMUTAGENIC ACTIVITY OF DNA DAMAGE-BINDING PROTEINS MEDIATED BY DIRECT INHIBITION OF TRANSLESION REPLICATION

DNA lesions that block replication can be bypassed in Escherichia coli by a special DNA synthesis process termed translesion replication, Th is process is mutagenic due to the miscoding nature of the DNA lesions , We report that the repair enzyme formamido-pyrimidine DNA glycosylas e and the general DNA damage recognition protein UvrA each inhibit spe cifically translesion replication through an abasic site analog by pur ified DNA polymerases I and II, and DNA polymerase III (alpha subunit) from E. coli. In vice experiments suggest that a similar inhibitory m echanism prevents at least 70% of the mutations caused by ultraviolet light DNA lesions in E. coli. These results suggest that DNA damage-bi nding proteins regulate mutagenesis by a novel mechanism that involves direct inhibition of translesion replication. This mechanism provides anti-mutagenic defense against DNA lesions that have escaped DNA repa ir.