A CHECKPOINT REGULATES THE RATE OF PROGRESSION THROUGH S-PHASE IN SACCHAROMYCES-CEREVISIAE IN RESPONSE TO DNA-DAMAGE

We demonstrate that in S. cerevisiae the rate of ongoing S phase is slowed when the DNA is subjected to alkylation. Slowing of replication is dependent on the MEC1 and RAD53 genes, indicating that lesions alone do not slow replication in vivo and that the slowing is an active process. While it has been shown that a MEC1- and RAD53-dependent checkpoint responds to blocked replication or DNA damage by inhibiting the onset of mitosis, we demonstrate that this checkpoint must also have an additional target within S phase that controls replication rate. MEC1 is a homolog of the human ATM gene, which is mutated in ataxia telangiectasia (AT) patients. Like mec1 yeast, AT cells are characterized by damage-resistant DNA synthesis, highlighting the congruence of the yeast and mammalian systems.