The function and regulation of budding yeast Swe1 in response to interrupted DNA synthesis.

Periodically regulated cyclin-dependent kinase (Cdk) is required for DNA synthesis and mitosis. Hydroxyurea (HU) inhibits DNA synthesis by depleting dNTPs, the basic unit for DNA synthesis. HU treatment triggers the S-phase checkpoint, which arrests cells at S-phase, inhibits late origin firing and stabilizes replication forks. Using budding yeast as a ...
model system, we found that Swe1, a negative regulator of Cdk, appears at S-phase and accumulates in HU treatment cells. Interestingly, this accumulation is not dependent on S-phase checkpoint. Deltahsl1, Deltahsl7, and cdc5-2 mutants, which have defects in Swe1 degradation, show HU sensitivity because of high Swe1 protein levels. We further demonstrated that their HU sensitivity is not a result of DNA damage accumulation or incomplete DNA synthesis; instead the sensitivity is due to their dramatically delayed recovery from HU-induced S-phase arrest. Strikingly, our in vivo data indicate that Swe1 inhibits the kinase activity of Clb2-Cdk1, but not that of Clb5-Cdk1. Therefore, S-phase accumulated Swe1 prevents Clb2-Cdk1-mediated mitotic activities, but has little effects on Clb5-Cdk1-associated S-phase progression.
Mesh Terms:
CDC2 Protein Kinase, Cell Cycle, Cell Cycle Proteins, Cyclin-Dependent Kinases, Cyclins, DNA Replication, Electrophoresis, Gel, Pulsed-Field, Gene Expression Regulation, Enzymologic, Gene Expression Regulation, Fungal, Hydroxyurea, Kinetics, Mitosis, Protein-Tyrosine Kinases, Saccharomyces cerevisiae Proteins, Schizosaccharomyces, Schizosaccharomyces pombe Proteins
Mol. Biol. Cell
Date: Jun. 01, 2006
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