Temporospatial Coordination of Meiotic DNA Replication and Recombination via DDK Recruitment to Replisomes

• Local replication timing dictates meiotic DSB timing (replication-DSB coordination)
• Tof1/Csm3 recruits DDK to moving replication forks to promote Mer2 phosphorylation
• Mer2 phosphorylation in the fork’s wake triggers recruitment of other DSB proteins
• Replication-associated phosphorylation establishes replication-DSB coordination

SummaryIt has been long appreciated that, during meiosis, DNA replication is coordinated with the subsequent formation of the double-strand breaks (DSBs) that initiate recombination, but a mechanistic understanding of this process was elusive. We now show that, in yeast, the replisome-associated components Tof1 and Csm3 physically associate with the Dbf4-dependent Cdc7 kinase (DDK) and recruit it to the replisome, where it phosphorylates the DSB-promoting factor Mer2 in the wake of the replication fork, synchronizing replication with an early prerequisite for DSB formation. Recruiting regulatory kinases to replisomes may be a general mechanism to ensure spatial and temporal coordination of replication with other chromosomal processes.

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