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The spindle checkpoint, APC/C(Cdc20), and APC/C(Cdh1) play distinct roles in connecting mitosis to S phase

Linda Clijsters1, Janneke Ogink, Rob Wolthuis

  • 1Division of Cell Biology I (B5), The Netherlands Cancer Institute (NKI-AvL), 1066 CX Amsterdam, Netherlands. l.clijsters@nki.nl

The Journal of Cell Biology
|June 19, 2013
PubMed

Insights

The spindle checkpoint and APC/C complexes control DNA replication licensing by regulating Cdt1, geminin, and Cdc6. This ensures proper cell cycle progression and timely S phase entry in proliferating cells.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Genetics

Background:

  • DNA replication requires licensing by Cdt1 and Cdc6.
  • Geminin and mitotic cyclin activity inhibit Cdt1 during S phase and mitosis.
  • Preventing re-replication is crucial for maintaining genomic stability.

Purpose of the Study:

  • To investigate the role of the spindle checkpoint and APC/C in regulating DNA replication licensing factors.
  • To elucidate the sequential degradation of geminin and Cdc6 during mitosis.
  • To understand how Cdt1 accumulation in mitosis promotes S phase onset.

Main Methods:

  • Investigated geminin as a target of the spindle checkpoint and APC/C(Cdc20).
  • Analyzed the simultaneous degradation of cyclin B1 and geminin during metaphase.
  • Examined the role of APC/C(Cdh1) in Cdc6 degradation and Cdt1 stability.

Main Results:

  • Geminin is degraded simultaneously with cyclin B1 by APC/C(Cdc20) during metaphase.
  • This degradation allows Cdt1 accumulation on segregating sister chromatids.
  • APC/C(Cdh1) subsequently degrades Cdc6, while Cdt1 remains stable until replication-coupled degradation.

Conclusions:

  • The spindle checkpoint, APC/C(Cdc20), and APC/C(Cdh1) act sequentially to regulate licensing factors.
  • This precise timing ensures licensing inhibitors disappear as Cdt1 and Cdc6 levels peak.
  • Proliferating cells utilize a mitotic window before Cdc6 degradation for earlier S phase entry.

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