S-PHASE DNA-DAMAGE CHECKPOINT IN BUDDING YEAST

wEukaryotic cells must be able to coordinate DNA repair, replication a nd cell cycle progression in response to DNA damage. A failure to acti vate the checkpoints which delay the cell cycle in response to interna l and external cues and to repair the DNA lesions results in an increa se in genetic instability and cancer predisposition, The use of the ye ast Saccharomyces cerevisiae has been invaluable in isolating many of the genes required for the DNA damage response, although the molecular mechanisms which couple this regulatory pathway to different DNA tran sactions are still largely unknown. In analogy with prokaryotes, we pr opose that DNA strand breaks, caused by genotoxic agents or by replica tion-related lesions, trigger a replication coupled repair mechanism, dependent upon recombination, which is induced by the checkpoint actin g during S-phase.