The DNA damage effector Chk1 kinase regulates Cdc14B nucleolar shuttling during cell cycle progression

Sirisha Peddibhotla, Zhubo Wei, Rao Papineni, Micheal H. Lam, Jeffrey M. Rosen, Pumin Zhang

Research output: Contribution to journalArticle

12 Scopus citations

Abstract

Chk1 is a critical effector of DNA damage checkpoints necessary for the maintenance of chromosome integrity during cell cycle progression. Here we report, that Chk1 co-localized with the nucleolar marker, fibrillarin in response to radiationinduced DNA damage in human cells. Interestingly, in vitro studies using GST pull down assays identified the dualspecificity serine/threonine nucleolar phosphatase Cdc14B as a Chk1 substrate. Furthermore, Chk1, but not a kinase-dead Chk1 control, was shown to phosphorylate Cdc14B using an in vitro kinase assay. Co-immunoprecipitation experiments using exogenous Cdc14B transfected into human cells confirmed the interaction of Cdc14B and Chk1 during cell cycle. In addition, reduction of Chk1 levels via siRNA or UCN-01 treatment demonstrated that Chk1 activation following DNA damage was required for Cdc14B export from the nucleolus. These studies have revealed a novel interplay between Chk1 kinase and Cdc14B phosphatase involving radiation-induced nucleolar shuttling to facilitate error-free cell cycle progression and prevent genomic instability.

Original languageEnglish (US)
Pages (from-to)671-679
Number of pages9
JournalCell Cycle
Volume10
Issue number4
DOIs
StatePublished - Feb 15 2011

Keywords

  • Cdc14B
  • Cell cycle
  • Chk1
  • DNA damage
  • Genomic instabiliy
  • Nucleoli

ASJC Scopus subject areas

  • Molecular Biology
  • Developmental Biology
  • Cell Biology

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