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S-phase-promoting cyclin-dependent kinases prevent re-replication by inhibiting the transition of replication origins

C Dahmann1, J F Diffley, K A Nasmyth

  • 1I.M.P. Research Institute of Molecular Pathology, Vienna, Austria.

Current Biology : CB
|November 1, 1995
PubMed
Abstract

Insights

Cyclin B-CDK complexes prevent DNA re-replication by inhibiting replication origins. This ensures DNA replication occurs only once per cell cycle, linking S phase to M phase completion.

Area of Science:

  • Cell cycle regulation
  • Molecular biology
  • Yeast genetics

Background:

  • Cell cycle progression relies on cyclin-CDK complexes.
  • Previously, cyclins were thought to dictate S or M phase.
  • B-type cyclins in yeast can function in both S and M phases.

Purpose of the Study:

  • Investigate the role of cyclin B-CDK complexes in preventing DNA re-replication.
  • Understand the regulation of DNA replication origins.
  • Clarify the link between S phase and M phase.

Main Methods:

  • Genetic analysis of Saccharomyces cerevisiae mutants (sim1, sim2).
  • Assaying cyclin kinase activity during cell cycle arrest.
  • Manipulating gene expression (CLB5) and protein activity (p40SIC1).

Main Results:

  • Mutants lacking CLB1-CLB4 initiate DNA replication but not mitosis.
  • SIM1/SIM2 mutants allow extra DNA replication rounds.
  • Clb5 kinase activity, crucial for S phase, is maintained in G2-arrested cells of sim mutants.
  • CLB5 overexpression prevents re-replication.
  • Inhibiting cyclin B-CDK kinases induces a pre-replicative state in G2/M-arrested cells.

Conclusions:

  • S-phase cyclin B-CDK complexes inhibit replication origin re-activation.
  • This mechanism ensures origins fire only once per cell cycle.
  • The model explains S phase dependency on M phase completion.

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