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USP29 controls the stability of checkpoint adaptor Claspin by deubiquitination

Oncogene volume 34, pages 1058–1063 (2015)Cite this article

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Abstract

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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Acknowledgements

We are grateful to V Smits for careful reading of the manuscript. We thank G Marfany, JW Harper and D Bohmann for helpful reagents. This work was supported by grants from the Spanish MINECO (SAF2010-22357, CONSOLIDER-Ingenio 2010 CDS2007-0015).

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Author notes

  1. Y Martín and E Cabrera: These authors contributed equally to this work.

Authors and Affiliations

  1. Unidad de Investigación, Hospital Universitario de Canarias, Instituto de Tecnologías Biomédicas,, La Laguna, Tenerife, Spain

    Y Martín, E Cabrera, H Amoedo, S Hernández-Pérez, R Domínguez-Kelly & R Freire

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  1. Y Martín
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  2. E Cabrera
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  3. H Amoedo
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  4. S Hernández-Pérez
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  5. R Domínguez-Kelly
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  6. R Freire
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Correspondence to R Freire.

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Martín, Y., Cabrera, E., Amoedo, H. et al. USP29 controls the stability of checkpoint adaptor Claspin by deubiquitination. Oncogene 34, 1058–1063 (2015). https://doi.org/10.1038/onc.2014.38

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