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CCDC98 targets BRCA1 to DNA damage sites

Nature Structural & Molecular Biology volume 14, pages 716720 (2007) | Download Citation

Abstract

Breast cancer-1 (BRCA1) participates in the DNA damage response. However, the mechanism by which BRCA1 is recruited to DNA damage sites remains elusive. Recently, we have demonstrated that a ubiquitin-binding protein, RAP80, is required for DNA damage–induced BRCA1 translocation. Here we identify another component, CCDC98, in the BRCA1–RAP80 complex. CCDC98 mediates BRCA1's association with RAP80. Moreover, CCDC98 controls both DNA damage–induced formation of BRCA1 foci and BRCA1-dependent G2/M checkpoint activation. Together, our results demonstrate that CCDC98 is a BRCA1 binding partner that mediates BRCA1 function in response to DNA damage.

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Acknowledgements

We thank C. Chen and L. Ye for technical support, and L. Lu for manuscript proofreading. This work was supported by the US Department of Defense Breast Cancer Research Program, the Ovarian Cancer Research Fund and the University of Michigan Cancer Center. X.Y. is the recipient of an American Association for Cancer Research–Susan G. Komen for the Cure Career Development Award for Breast Cancer Research.

Author information

Affiliations

  1. Division of Molecular Medicine and Genetics, Department of Internal Medicine, University of Michigan Medical School, 109 Zina Pitcher Place, BSRB 1520, Ann Arbor, Michigan 48109, USA.

    • Zixing Liu
    • , Jiaxue Wu
    •  & Xiaochun Yu

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Contributions

X.Y. purified proteins and identified the BRCA1–CCDC98–RAP80 complex. Z.L. and J.W. analyzed the protein interactions of this complex. Z.L. and X.Y. examined the role of CCDC98 in the formation of DNA damage–induced protein foci and G2/M checkpoint activation. X.Y. drafted the manuscript. All the authors read and approved the final manuscript.

Competing interests

The authors declare no competing financial interests.

Corresponding author

Correspondence to Xiaochun Yu.

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DOI

https://doi.org/10.1038/nsmb1279

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