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 language | English (US) |
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Pages (from-to) | 671-679 |
Number of pages | 9 |
Journal | Cell Cycle |
Volume | 10 |
Issue number | 4 |
DOIs | |
State | Published - Feb 15 2011 |
Keywords
- Cdc14B
- Cell cycle
- Chk1
- DNA damage
- Genomic instabiliy
- Nucleoli
ASJC Scopus subject areas
- Molecular Biology
- Developmental Biology
- Cell Biology