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

Albert Serra-Cardona, Chuanhe Yu, Xinmin Zhang, Xu Hua, Yuan Yao, Jiaqi Zhou, Haiyun Gan, Zhiguo Zhang

Research output: Contribution to journalArticlepeer-review

11 Scopus citations

Abstract

In response to DNA replication stress, DNA replication checkpoint kinase Mec1 phosphorylates Mrc1, which in turn activates Rad53 to prevent the generation of deleterious single-stranded DNA, a process that remains poorly understood. We previously reported that lagging-strand DNA synthesis proceeds farther than leading strand in rad53-1 mutant cells defective in replication checkpoint under replication stress, resulting in the exposure of long stretches of the leading-strand templates. Here, we show that asymmetric DNA synthesis is also observed in mec1-100 and mrc1-AQ cells defective in replication checkpoint but, surprisingly, not in mrc1∆ cells in which both DNA replication and checkpoint functions of Mrc1 are missing. Furthermore, depletion of either Mrc1 or its partner, Tof1, suppresses the asymmetric DNA synthesis in rad53-1 mutant cells. Thus, the DNA replication checkpoint pathway couples leading- and lagging-strand DNA synthesis by attenuating the replication function of Mrc1-Tof1 under replication stress.

Original languageEnglish (US)
Article numbere2109334118
JournalProceedings of the National Academy of Sciences of the United States of America
Volume118
Issue number38
DOIs
StatePublished - Sep 21 2021

Bibliographical note

Publisher Copyright:
© 2021 National Academy of Sciences. All rights reserved.

Keywords

  • Asymmetric DNA synthesis
  • Deleterious ssDNA
  • Mrc1
  • Rad53
  • Replication stress

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