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.

Related Concept Videos

S-Cdk Initiates DNA Replication02:38

S-Cdk Initiates DNA Replication

The cell cycle is a series of events leading to DNA duplication followed by the division of cell content to form two daughter cells. The cell cycle progresses in four stages—the cell increases in size (gap 1 or G1-phase), duplicates its DNA (synthesis or S-phase), prepares to divide (gap 2 or G2-phase), and divides (mitosis or M-phase).
Two states at the origin of replication
In eukaryotes, the initiation of replication occurs at many sites on the chromosomes, called the origins of...
4.8K
S-Cdk Initiates DNA Replication02:38

S-Cdk Initiates DNA Replication

3.0K
Inhibition of Cdk Activity02:34

Inhibition of Cdk Activity

The orderly progression of the cell cycle depends on the activation of Cdk protein by binding to its cyclin partner. However, the cell cycle must be restricted when undergoing abnormal changes. Most cancers correlate to the deregulated cell cycle, and since Cdks are a central component of the cell cycle, Cdk inhibitors are extensively studied to develop anticancer agents. For instance, cyclin D associates with several Cdks, such as Cdk 4/6, to form an active complex. The cyclin D-Cdk4/6 complex...
4.8K
M-Cdk Drives Transition Into Mitosis02:15

M-Cdk Drives Transition Into Mitosis

Checkpoints throughout the cell cycle serve as safeguards and gatekeepers, allowing the cell cycle to progress in favorable conditions and slow or halt it in problematic ones. This regulation is known as the cell cycle control system.
Cyclin-dependent kinases, or Cdks, work in concert with cyclins to control cell cycle transitions. M-Cdk, a complex of Cdk1 bound to M cyclin, is a well-known example of this coordinated control that drives the transition from the G2 to the M phase.
M cyclin...
5.3K
Meiosis II02:02

Meiosis II

Meiosis II entails cell division and segregation of the sister chromatids, resulting in the production of four unique haploid gametes. The steps for meiosis II are similar to mitosis, except that meiosis II occurs in haploid cells, whereas mitosis occurs in diploid cells.
The timing and cell division patterns of meiosis differ between males and females. In male meiosis, the centrosomes are part of the formation of the meiotic spindle. However, in oocytes, including that of humans, Drosophila,...
32.7K