Cdc18p can block mitosis by two independent mechanisms

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Studying Cell Cycle-regulated Gene Expression by Two Complementary Cell Synchronization Protocols
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Studying Cell Cycle-regulated Gene Expression by Two Complementary Cell Synchronization Protocols

Published on: June 6, 2017

E Greenwood1, H Nishitani, P Nurse

  • 1Cell Cycle Laboratory, Imperial Cancer Research Fund, London, WC2A 3PX, UK. e.greenwood@icrf.icnet.uk.

Journal of Cell Science
|September 18, 1998
PubMed

Insights

The cdc18 protein

Area of Science:

  • Cell Cycle Regulation
  • Genomic Stability
  • Molecular Biology

Background:

  • The DNA replication checkpoint is crucial for maintaining genomic integrity by preventing premature mitosis.
  • In Schizosaccharomyces pombe, this checkpoint involves the phosphorylation of cdc2p to inhibit mitosis.
  • The cdc18 gene plays a vital role in initiating S phase and establishing the DNA replication checkpoint.

Purpose of the Study:

  • To investigate the distinct roles of the N-terminal and C-terminal domains of the cdc18 protein in cell cycle control.
  • To elucidate the mechanisms by which cdc18p regulates the DNA replication checkpoint and mitosis.
  • To determine the relationship between cdc18p domains and known checkpoint and kinase components.

Main Methods:

  • Functional analysis of cdc18p N-terminal and C-terminal domains.
  • Investigating the genetic interactions between cdc18p and DNA replication checkpoint genes (rad1, rad3, rad9, rad17, hus1, cut5).
  • Assessing the requirement of wee1p/mik1p tyrosine kinases for cdc18p-mediated mitotic inhibition.
  • In vivo association studies between cdc18p and cdc2p/cdc13p.

Main Results:

  • The C-terminus of cdc18p initiates DNA replication and mediates checkpoint function, acting upstream of checkpoint genes and requiring wee1p/mik1p.
  • The N-terminus of cdc18p also inhibits mitosis but functions independently of the DNA replication checkpoint genes and wee1p/mik1p.
  • The N-terminus of cdc18p directly binds to the cdc2p/cdc13p mitotic kinase in vivo.

Conclusions:

  • The cdc18 protein possesses distinct functional domains that differentially regulate the cell cycle.
  • The C-terminal domain integrates with the canonical DNA replication checkpoint pathway.
  • The N-terminal domain bypasses normal checkpoint controls by directly interacting with the mitotic kinase, potentially representing an unphysiological mechanism.

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