title: S-phase cyclins are required for a stable arrest at metaphase.
abstract: A critical DNA damage checkpoint in Saccharomyces cerevisiae is an arrest at the metaphase stage of mitosis. Here we show that the S-phase cyclins Clb5 and Clb6 are required for this arrest. Strains lacking Clb5 and Clb6 are hypersensitive to DNA damage. Furthermore, in the presence of the DNA alkylating agent methyl methanesulfonate (MMS) over 50% of clb5 clb6 mutants by-passed the metaphase checkpoint and arrested instead with separated sister chromatids. Levels of Pds1, an inhibitor of anaphase that accumulates following DNA damage, were similar in the wild-type and mutant strains following MMS treatment. Furthermore, unlike wild-type cells, clb5 clb6 mutants undergo nuclear division despite the presence of nuclear non-degradable Pds1. Our results suggest a novel role for the S-phase cyclins Clb5 and Clb6 in maintaining sister chromatid cohesion during a metaphase arrest, perhaps by regulating Pds1 activity.
authors.affiliation: Howard Hughes Medical Institute and Department of Genetics, University of Pennsylvania Medical School, Room 445 CRB, 415 Curie Blvd, Philadelphia, Pennsylvania 19104, USA.
authors.forename: M A
authors.initials: MA
authors.lastname: Meyn
authors.forename: S L
authors.initials: SL
authors.lastname: Holloway
mesh_terms: D018906:Antineoplastic Agents, Alkylating / Q000494:pharmacology; D018797:Cell Cycle Proteins / Q000378:metabolism; D002467:Cell Nucleus / Q000378:metabolism; D064447:Checkpoint Kinase 2; D002868:Chromosomal Proteins, Non-Histone; D019926:Cyclin B / Q000378:metabolism*; D004249:DNA Damage; D005656:Fungal Proteins / Q000378:metabolism; D017930:Genes, Reporter; D008677:Metaphase / Q000187:drug effects; D008741:Methyl Methanesulfonate / Q000494:pharmacology; D008938:Mitosis / Q000187:drug effects; D009687:Nuclear Proteins; D010750:Phosphoproteins; D011494:Protein Kinases / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D016196:S Phase / Q000187:drug effects; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000502:physiology*; D029701:Saccharomyces cerevisiae Proteins
chemical_list: D018906:Antineoplastic Agents, Alkylating; C076558:CLB5 protein, S cerevisiae; C095227:CLB6 protein, S cerevisiae; D018797:Cell Cycle Proteins; D002868:Chromosomal Proteins, Non-Histone; D019926:Cyclin B; D005656:Fungal Proteins; C490529:MCD1 protein, S cerevisiae; D009687:Nuclear Proteins; D010750:Phosphoproteins; D011993:Recombinant Fusion Proteins; D029701:Saccharomyces cerevisiae Proteins; D008741:Methyl Methanesulfonate; D011494:Protein Kinases; D064447:Checkpoint Kinase 2; D017346:Protein Serine-Threonine Kinases; C067022:RAD53 protein, S cerevisiae