Proteins in the Nutrient-Sensing and DNA damage checkpoint pathways cooperate to restrain mitotic progression following DNA damage

Jennifer S. Searle, Matthew D. Wood, Mandeep Kaur, David V. Tobin, Yolanda Sanchez

Research output: Contribution to journalArticle

14 Scopus citations

Abstract

Checkpoint pathways regulate genomic integrity in part by blocking anaphase until all chromosomes have been completely replicated, repaired, and correctly aligned on the spindle. In Saccharomyces cerevisiae, DNA damage and mono-oriented or unattached kinetochores trigger checkpoint pathways that bifurcate to regulate both the metaphase to anaphase transition and mitotic exit. The sensor-associated kinase, Mec1, phosphorylates two downstream kinases, Chk1 and Rad53. Activation of Chk1 and Rad53 prevents anaphase and causes inhibition of the mitotic exit network. We have previously shown that the PKA pathway plays a role in blocking securin and Clb2 destruction following DNA damage. Here we show that the Mec1 DNA damage checkpoint regulates phosphorylation of the regulatory (R) subunit of PKA following DNA damage and that the phosphorylated R subunit has a role in restraining mitosis following DNA damage. In addition we found that proteins known to regulate PKA in response to nutrients and stress either by phosphorylation of the R subunit or regulating levels of cAMP are required for the role of PKA in the DNA damage checkpoint. Our data indicate that there is cross-talk between the DNA damage checkpoint and the proteins that integrate nutrient and stress signals to regulate PKA.

Original languageEnglish (US)
Article numbere1002176
JournalPLoS genetics
Volume7
Issue number7
DOIs
StatePublished - Jul 2011

ASJC Scopus subject areas

  • Ecology, Evolution, Behavior and Systematics
  • Molecular Biology
  • Genetics
  • Genetics(clinical)
  • Cancer Research

Fingerprint Dive into the research topics of 'Proteins in the Nutrient-Sensing and DNA damage checkpoint pathways cooperate to restrain mitotic progression following DNA damage'. Together they form a unique fingerprint.

  • Cite this