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USP29 controls the stability of checkpoint adaptor Claspin by deubiquitination
The DNA damage checkpoint is essential for the maintenance of genome integrity after genotoxic stress, and also for cell survival in eukaryotes. Claspin has a key role in the ATR (ATM and Rad3-related)-Chk1 branch of the DNA damage checkpoint and is also required for correct DNA replication. To achi...
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Published in: | Oncogene 2015-02, Vol.34 (8), p.1058-1063 |
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Main Authors: | , , , , , |
Format: | Article |
Language: | English |
Subjects: | |
Citations: | Items that this one cites Items that cite this one |
Online Access: | Get full text |
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Summary: | The DNA damage checkpoint is essential for the maintenance of genome integrity after genotoxic stress, and also for cell survival in eukaryotes. Claspin has a key role in the ATR (ATM and Rad3-related)-Chk1 branch of the DNA damage checkpoint and is also required for correct DNA replication. To achieve properly these functions, Claspin is tightly regulated by ubiquitinin-dependent proteasomal degradation, which controls Claspin levels in a DNA-damage- and cell-cycle-dependent manner. Here, we identified a new regulator of Claspin, the ubiquitin-specific peptidase 29, USP29. Downregulation of USP29 destabilizes Claspin, whereas its overexpression promotes an increase in Claspin levels. USP29 interacts with Claspin and is able to deubiquitinate it both in vivo and in vitro. Most importantly, USP29 knockdown results in an impaired phosphorylation of Chk1 after DNA damage and USP29-depleted cells show a major defect in the S-phase progression. With these results, we identified USP29 as a new player in the ATR-Chk1 pathway and the control of DNA replication. |
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ISSN: | 0950-9232 1476-5594 |
DOI: | 10.1038/onc.2014.38 |