title: Signaling pathways of replication stress in yeast.
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.
authors.affiliation: Institute of Human Genetics, CNRS UPR1142, University of Montpellier, Montpellier 34396, France.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Pardo
authors.affiliation: Institute for Integrative Biology of the Cell (I2BC), CNRS/CEA/Univ. Paris Sud, Université Paris-Saclay, Gif-sur-Yvette 91198, France.
authors.forename: Laure
authors.initials: L
authors.lastname: Crabbé
authors.affiliation: Institute of Human Genetics, CNRS UPR1142, University of Montpellier, Montpellier 34396, France.
authors.forename: Philippe
authors.initials: P
authors.lastname: Pasero
mesh_terms: D002453:Cell Cycle; D018797:Cell Cycle Proteins / Q000378:metabolism; D064447:Checkpoint Kinase 2 / Q000378:metabolism; D004249:DNA Damage; D004260:DNA Repair; D004261:DNA Replication; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000235:genetics* / Q000502:physiology*; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D018797:Cell Cycle Proteins; D047908:Intracellular Signaling Peptides and Proteins; C441579:MRC1 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; C069930:rad9 protein; D064447:Checkpoint Kinase 2; C088937:MEC1 protein, S cerevisiae; D017346:Protein Serine-Threonine Kinases; C067022:RAD53 protein, S cerevisiae
keywords: DNA replication; checkpoints; genomic instability