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CDK phosphorylation of SLD-2 is required for replication initiation and germline development in C. elegans

Vincent Gaggioli1, Eva Zeiser, David Rivers

  • 1Wellcome Trust/Cancer Research UK Gurdon Institute, 2 Department of Genetics, and 3 Department of Zoology, University of Cambridge, Cambridge CB2 1QN, England, UK.

The Journal of Cell Biology
|February 19, 2014
PubMed

Insights

Cyclin-dependent kinase (CDK) controls cell proliferation. In worms, CDK phosphorylation of SLD-2 is essential for DNA replication initiation and germline proliferation, revealing a key metazoan CDK function.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Developmental Biology

Background:

  • Cyclin-dependent kinase (CDK) is crucial for eukaryotic proliferation control.
  • The precise role of CDK in metazoan cell cycle and developmental transitions remains unclear.

Purpose of the Study:

  • Identify and characterize the Sld2 orthologue (SLD-2) in Caenorhabditis elegans.
  • Investigate the role of CDK-mediated phosphorylation of SLD-2 in DNA replication and development.

Main Methods:

  • Identification of SLD-2 orthologues in C. elegans.
  • Functional analysis of SLD-2 in embryonic development.
  • In vivo characterization of SLD-2 as a CDK target.
  • Mutation and phosphomimicking studies of SLD-2 phosphorylation sites.

Main Results:

  • SLD-2 is essential for DNA replication initiation and CDC-45 nuclear retention in C. elegans embryos.
  • SLD-2 is a CDK target, and its phosphorylation regulates interaction with MUS-101.
  • CDK phosphorylation of SLD-2 is critical for C. elegans viability.
  • Timely CDK phosphorylation of SLD-2 is required for normal germline proliferation.

Conclusions:

  • CDK plays an essential role in metazoan proliferation.
  • Regulated SLD-2 phosphorylation by CDK is a critical developmental control mechanism.

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