Anti-mutagenic 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. This process is mutagenic due to the miscoding nature of the DNA lesions. We report that the repair enzyme formamido-pyrimidine DNA glycosylase and the general DNA damage recognition protein UvrA each inhibit specifically translesion replication through an abasic site analog by purified DNA polymerases I and II, and DNA polymerase III (alpha subunit) from E. coli. In vivo experiments suggest that a similar inhibitory mechanism prevents at least 70% of the mutations caused by ultraviolet light DNA lesions in E. coli. These results suggest that DNA damage-binding 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 repair.
Paz-Elizur
T
T
Department of Biological Chemistry, Faculty of Biochemistry, Weizmann Institute of Science, Rehovot 76100, Israel.
Barak
Y
Y
Livneh
Z
Z
D000251:Adenosine Triphosphatases / Q000378:metabolism; D016587:Antimutagenic Agents / Q000378:metabolism*; D001426:Bacterial Proteins / Q000378:metabolism; D004249:DNA Damage; D004261:DNA Replication; D004277:DNA, Single-Stranded / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism*; D043382:DNA-Formamidopyrimidine Glycosylase; D004255:Deoxyribodipyrimidine Photo-Lyase / Q000378:metabolism; D029968:Escherichia coli Proteins; D016296:Mutagenesis; D009699:N-Glycosyl Hydrolases / Q000378:metabolism; D014466:Ultraviolet Rays
D016587:Antimutagenic Agents; D001426:Bacterial Proteins; D004277:DNA, Single-Stranded; D004268:DNA-Binding Proteins; D029968:Escherichia coli Proteins; D009699:N-Glycosyl Hydrolases; D043382:DNA-Formamidopyrimidine Glycosylase; C468610:DNA-formamidopyrimidine glycosylase, E coli; C068631:UvrA protein, E coli; D000251:Adenosine Triphosphatases; D004255:Deoxyribodipyrimidine Photo-Lyase