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 sl owed when the DNA is subjected to alkylation. Slowing of replication i s dependent on the MEC1 and RAD53 genes, indicating that lesions alone do not slow replication in vivo and that the slowing is an active pro cess. While it has been shown that a MEC1- and RAD53-dependent checkpo int responds to blocked replication or DNA damage by inhibiting the on set 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 telangi ectasia (AT) patients. Like mec1 yeast, AT cells are characterized by damage-resistant DNA synthesis, highlighting the congruence of the yea st and mammalian systems.