Signaling pathways of replication stress in yeast

FEMS Yeast Res. 2017 Mar 1;17(2). doi: 10.1093/femsyr/fow101.

Abstract

Eukaryotic cells activate the S-phase checkpoint in response to a variety of events affecting the progression of replication forks, collectively referred to as replication stress. This signaling pathway is divided in two branches: the DNA damage checkpoint (DDC) and the DNA replication checkpoint (DRC). Both pathways are activated by the sensor kinase Mec1 and converge on the effector kinase Rad53. However, the DDC operates throughout the cell cycle and depends on the checkpoint mediator Rad9 to activate Rad53, whereas the DRC is specific to S phase and is mediated by Mrc1 and other fork components to signal replication impediments. In this review, we summarize current knowledge on these two pathways, with a focus on the budding yeast Saccharomyces cerevisiae, in which many important aspects of the replication stress response were discovered. We also discuss the differences and similarities between DDC and DRC and speculate on how these pathways cooperate to ensure the complete and faithful duplication of the yeast genome under various replication stress conditions.

Keywords: DNA replication; checkpoints; genomic instability.

Publication types

  • Review

MeSH terms

  • Cell Cycle
  • Cell Cycle Proteins / metabolism
  • Checkpoint Kinase 2 / metabolism
  • DNA Damage*
  • DNA Repair*
  • DNA Replication*
  • Intracellular Signaling Peptides and Proteins / metabolism
  • Protein-Serine-Threonine Kinases / metabolism
  • Saccharomyces cerevisiae / genetics*
  • Saccharomyces cerevisiae / physiology*
  • Saccharomyces cerevisiae Proteins / metabolism
  • Signal Transduction*

Substances

  • Cell Cycle Proteins
  • Intracellular Signaling Peptides and Proteins
  • MRC1 protein, S cerevisiae
  • Saccharomyces cerevisiae Proteins
  • rad9 protein
  • Checkpoint Kinase 2
  • MEC1 protein, S cerevisiae
  • Protein-Serine-Threonine Kinases
  • RAD53 protein, S cerevisiae