title: DNA replication and spindle checkpoints cooperate during S phase to delay mitosis and preserve genome integrity.
abstract: Deoxyribonucleic acid (DNA) replication and chromosome segregation must occur in ordered sequence to maintain genome integrity during cell proliferation. Checkpoint mechanisms delay mitosis when DNA is damaged or upon replication stress, but little is known on the coupling of S and M phases in unperturbed conditions. To address this issue, we postponed replication onset in budding yeast so that DNA synthesis is still underway when cells should enter mitosis. This delayed mitotic entry and progression by transient activation of the S phase, G2/M, and spindle assembly checkpoints. Disabling both Mec1/ATR- and Mad2-dependent controls caused lethality in cells with deferred S phase, accompanied by Rad52 foci and chromosome missegregation. Thus, in contrast to acute replication stress that triggers a sustained Mec1/ATR response, multiple pathways cooperate to restrain mitosis transiently when replication forks progress unhindered. We suggest that these surveillance mechanisms arose when both S and M phases were coincidently set into motion by a unique ancestral cyclin-Cdk1 complex.
authors.affiliation: Institute of Molecular Genetics, Centre National de la Recherche Scientifique Unité Mixte de Recherche 5535 and University of Montpellier, 34293 Montpellier, France.
authors.forename: Maria M
authors.initials: MM
authors.lastname: Magiera
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Gueydon
authors.forename: Etienne
authors.initials: E
authors.lastname: Schwob
mesh_terms: D059447:Cell Cycle Checkpoints; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D020090:Chromosome Segregation; D018844:Cyclin-Dependent Kinases / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D004249:DNA Damage; D004261:DNA Replication / Q000502:physiology*; D005656:Fungal Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D042822:Genomic Instability; D016196:S Phase; D004718:Saccharomycetales; D008941:Spindle Apparatus / Q000502:physiology*
chemical_list: D018797:Cell Cycle Proteins; D005656:Fungal Proteins; D018844:Cyclin-Dependent Kinases