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Cell Cycle. 2011 Feb 15;10(4):671-9. Epub 2011 Feb 15.

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

Author information

1
Department of Molecular and Cell Biology, Baylor College of Medicine, Houston, TX USA.

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 radiation-induced DNA damage in human cells. Interestingly, in vitro studies using GST pull down assays identified the dual-specificity 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.

PMID:
21301228
PMCID:
PMC3174002
DOI:
10.4161/cc.10.4.14901
[Indexed for MEDLINE]
Free PMC Article

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