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Cdc14b regulates mammalian RNA polymerase II and represses cell cycle transcription

María Guillamot1, Eusebio Manchado, Massimo Chiesa

  • 1Cell Division and Cancer Group, Spanish National Cancer Research Center (CNIO), E-28029 Madrid, Spain.

Scientific Reports
|February 23, 2012
PubMed

Insights

The phosphatase Cdc14b controls cell cycle progression in mammals. Its absence causes premature DNA replication and mitosis by affecting RNA polymerase II transcription.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Biochemistry

Background:

  • Cdc14 is a vital phosphatase in yeast cell cycle regulation.
  • The function of Cdc14 in the mammalian cell cycle is not well understood.

Purpose of the Study:

  • To investigate the role of Cdc14b in the mammalian cell cycle.
  • To elucidate the molecular mechanisms by which Cdc14b influences cell cycle progression.

Main Methods:

  • Generation and analysis of Cdc14b-knockout mouse cells.
  • Assessment of cell cycle progression, DNA replication, and mitosis.
  • Analysis of RNA polymerase II C-terminal domain (CTD) phosphorylation.
  • Investigation of epigenetic modifications and gene transcription.

Main Results:

  • Cdc14b-knockout cells showed unscheduled entry into DNA replication and mitosis from quiescence.
  • Cdc14b was identified as a phosphatase for Ser5 on the RNA polymerase II CTD.
  • Loss of Cdc14b led to increased CTD-Ser5 phosphorylation and transcriptional induction of cell cycle regulators.
  • These changes were associated with epigenetic modifications indicative of active chromatin.

Conclusions:

  • Mammalian Cdc14b plays a crucial role in regulating the cell cycle.
  • Cdc14b controls cell cycle entry by modulating RNA polymerase II CTD phosphorylation and gene transcription.
  • These findings reveal a novel function for Cdc14 phosphatases in coordinating cell cycle progression and transcriptional control.

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