Regulation of DNA replication fork progression through damaged DNA by the Mec1/Rad53 checkpoint

摘要: The checkpoint kinase proteins Mec1 and Rad53 are required in the budding yeast, Saccharomyces cerevisiae, to maintain cell viability presence of drugs causing damage DNA or arrest replication forks. It is thought that they act by inhibiting cycle progression, allowing time for repair take place. also slow S phase progression response alkylation, although mechanism this its relative importance protecting cells from have not been determined. Here we show DNA-alkylating agent methyl methanesulphonate (MMS) profoundly reduces rate fork progression; however, moderation does require Mec1. accelerated mutants, therefore, primarily a consequence inappropriate initiation events. Wild-type ultimately complete MMS. In contrast, forks mutants collapse irreversibly at high rates. Moreover, cytotoxicity MMS occurs specifically when allowed enter with damage. Thus, preventing damage-induced catastrophe seems be primary which checkpoints preserve face alkylation.