Abstract
Eukaryotic cells activate cell cycle checkpoints in response to DNA damage. In Saccharomyces cerevisiae, the DNA damage response is achieved by the activation of the sensor kinases Mec1 and Tel1 and transmitted to the effector kinase Rad53. Rad9 and Mrc1 are thought to differentially mediate the activation of Rad53 depending on the cell cycle phase. Rad9 can respond to DNA lesions throughout the cell cycle, whereas Mrc1 responds to replication impediments in S phase. It was not clear if Rad9 and Mrc1 were triggering the same response to DNA damage occurring in S phase. By carefully studying the kinetics of activation of Rad53 by different types of replication stresses, we recently showed that Rad9 and Mrc1 cooperate in time and space to trigger a unique response to DNA damage in S phase. This primarily includes the control of both DNA replication initiation and elongation. After showing that Rad9 plays a preponderant role during S phase, the data presented here provocatively suggest that Mrc1 could also mediate the activation of Rad53 outside of S phase.