title: The yeast S phase checkpoint enables replicating chromosomes to bi-orient and restrain spindle extension during S phase distress.
abstract: The budding yeast S phase checkpoint responds to hydroxyurea-induced nucleotide depletion by preventing replication fork collapse and the segregation of unreplicated chromosomes. Although the block to chromosome segregation has been thought to occur by inhibiting anaphase, we show checkpoint-defective rad53 mutants undergo cycles of spindle extension and collapse after hydroxyurea treatment that are distinct from anaphase cells. Furthermore, chromatid cohesion, whose dissolution triggers anaphase, is dispensable for S phase checkpoint arrest. Kinetochore-spindle attachments are required to prevent spindle extension during replication blocks, and chromosomes with two centromeres or an origin of replication juxtaposed to a centromere rescue the rad53 checkpoint defect. These observations suggest that checkpoint signaling is required to generate an inward force involved in maintaining preanaphase spindle integrity during DNA replication distress. We propose that by promoting replication fork integrity under these conditions Rad53 ensures centromere duplication. Replicating chromosomes can then bi-orient in a cohesin-independent manner to restrain untimely spindle extension.
authors.affiliation: Department of Cell Biology and Neuroscience, University of California, Riverside, Riverside, CA 92521, USA. jeffbach@citrus.ucr.edu
authors.forename: Jeff
authors.initials: J
authors.lastname: Bachant
authors.forename: Shannon R
authors.initials: SR
authors.lastname: Jessen
authors.forename: Sarah E
authors.initials: SE
authors.lastname: Kavanaugh
authors.forename: Candida S
authors.initials: CS
authors.lastname: Fielding
mesh_terms: D000705:Anaphase / Q000235:genetics; D018797:Cell Cycle Proteins / Q000235:genetics; D002503:Centromere / Q000235:genetics; D064447:Checkpoint Kinase 2; D002868:Chromosomal Proteins, Non-Histone; D020090:Chromosome Segregation / Q000187:drug effects / Q000235:genetics; D002875:Chromosomes / Q000235:genetics*; D004247:DNA / Q000096:biosynthesis; D005656:Fungal Proteins; D018816:Genes, cdc / Q000187:drug effects / Q000502:physiology*; D006918:Hydroxyurea / Q000494:pharmacology; D018386:Kinetochores / Q000502:physiology; D008938:Mitosis / Q000187:drug effects / Q000235:genetics*; D009154:Mutation / Q000235:genetics; D009687:Nuclear Proteins / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000235:genetics; D016196:S Phase / Q000187:drug effects / Q000235:genetics*; D012441:Saccharomyces cerevisiae / Q000235:genetics*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics; D008941:Spindle Apparatus / Q000235:genetics*; D000097722:Cohesins
chemical_list: D018797:Cell Cycle Proteins; D064447:Checkpoint Kinase 2; D002868:Chromosomal Proteins, Non-Histone; D004247:DNA; D005656:Fungal Proteins; D006918:Hydroxyurea; D009687:Nuclear Proteins; D017346:Protein Serine-Threonine Kinases; D029701:Saccharomyces cerevisiae Proteins; D000097722:Cohesins; C067022:RAD53 protein, S cerevisiae