Mrc1 transduces signals of DNA replication stress to activate Rad53

Cells experiencing DNA replication stress activate a response pathway that delays entry into mitosis and promotes DNA repair and completion of DNA rep lication. The protein kinases ScRad53 and SpCds1 (in baker's and fission ye ast, respectively) are central to this pathway. We describe a conserved pro tein Mrc1, mediator of the replication checkpoint, required for activation of ScRad53 and SpCds1 during replication stress. mrc1 mutants are sensitive to hydroxyurea and have a checkpoint defect similar to rad53 and cds1 muta nts. Mrc1 may be the replicative counterpart of Rad9 and Crb2, which are re quired for activating ScRad53 and Chk1 in response to DNA damage.