S-phase cyclins are required for a stable arrest at metaphase.
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.
Mesh Terms:
Antineoplastic Agents, Alkylating, Cell Cycle Proteins, Cell Nucleus, Chromosomal Proteins, Non-Histone, Cyclin B, DNA Damage, Fungal Proteins, Genes, Reporter, Metaphase, Methyl Methanesulfonate, Mitosis, Nuclear Proteins, Phosphoproteins, Protein Kinases, Protein-Serine-Threonine Kinases, Recombinant Fusion Proteins, S Phase, Saccharomyces cerevisiae, Saccharomyces cerevisiae Proteins
Antineoplastic Agents, Alkylating, Cell Cycle Proteins, Cell Nucleus, Chromosomal Proteins, Non-Histone, Cyclin B, DNA Damage, Fungal Proteins, Genes, Reporter, Metaphase, Methyl Methanesulfonate, Mitosis, Nuclear Proteins, Phosphoproteins, Protein Kinases, Protein-Serine-Threonine Kinases, Recombinant Fusion Proteins, S Phase, Saccharomyces cerevisiae, Saccharomyces cerevisiae Proteins
Curr. Biol.
Date: Jan. 04, 2001
PubMed ID: 11137013
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