A mechanism for Rad53 to couple leading- and lagging-strand DNA synthesis under replication stress in budding yeast

Abstract

Significance During the S phase of the cell cycle, the DNA replication machinery accurately duplicates the genome in spite of numerous hurdles that cause replication stress. The replication checkpoint pathway deals with the replication stress, which, if left undealt with, can lead to fork collapse and genome instability, a process that remains poorly understood. Here, we show that the DNA checkpoint pathway couples leading- and lagging-strand DNA synthesis to prevent the generation of deleterious single-stranded DNA under replication stress by attenuating the replication function of Mrc1, a protein involved in both DNA replication and replication checkpoint, providing a mechanistic insight into how eukaryotic cells overcome replication stress.