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Two-Stage Mechanism For Activation Of The Dna Replication Checkpoint Kinase Cds1 In Fission Yeast, Xu Yong, Matthew Davenport, Thomas Kelly
Two-Stage Mechanism For Activation Of The Dna Replication Checkpoint Kinase Cds1 In Fission Yeast, Xu Yong, Matthew Davenport, Thomas Kelly
Matthew P Davenport
The DNA replication checkpoint is a complex signal transduction pathway, present in all eukaryotic cells, that functions to maintain genomic integrity and cell viability when DNA replication is perturbed. In Schizosaccharomyces pombe the major effector of the replication checkpoint is the protein kinase Cds1. Activation of Cds1 is known to require the upstream kinase Rad3 and the mediator Mrc1, but the biochemical mechanism of activation is not well understood. We report that the replication checkpoint is activated in two stages. In the first stage, Mrc1 recruits Cds1 to stalled replication forks by interactions between the FHA domain of Cds1 and …