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CCDC98 is a BRCA1-BRCT domain–binding protein involved in the DNA damage response

Nature Structural & Molecular Biology volume 14, pages 710–715 (2007)Cite this article

Abstract

The product of the breast cancer-1 gene, BRCA1, plays a crucial part in the DNA damage response through its interactions with many proteins, including BACH1, CtIP and RAP80. Here we identify a coiled-coil domain–containing protein, CCDC98, as a BRCA1-interacting protein. CCDC98 colocalizes with BRCA1 and is required for the formation of BRCA1 foci in response to ionizing radiation. Moreover, like BRCA1, CCDC98 has a role in radiation sensitivity and damage-induced G2/M checkpoint control. Together, these results suggest that CCDC98 is a mediator of BRCA1 function involved in the mammalian DNA damage response.

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Figure 1: Identification of CCDC98 as a BRCA1-binding protein.
Figure 2: Localization of CCDC98 in cells exposed to ionizing radiation.
Figure 3: Focus localization of CCDC98 depends on its N-terminal RAP80-binding region.
Figure 4: Requirement of CCDC98 for ionizing radiation–induced DNA damage response.

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Acknowledgements

We thank members of the Chen laboratory for helpful discussions and technical support. This work was supported in part by grants from the US National Institute of Health (RO1CA089239 to J.C.) and the US Department of Defense breast cancer Era of Hope Scholar Award (W81XWH-05-1-0470 to J.C.).

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  1. Hongtae Kim and Jun Huang: These authors contributed equally to this work.

Authors and Affiliations

  1. Department of Therapeutic Radiology, Yale University School of Medicine, P.O. Box 208040, New Haven, 06520, Connecticut, USA

    Hongtae Kim, Jun Huang & Junjie Chen

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  1. Hongtae Kim
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Contributions

H.K., J.H. and J.C. designed experiments and interpreted the data; H.K. and J.H. performed all experiments; H.K. and J.C. prepared the manuscript.

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Correspondence to Junjie Chen.

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The authors declare no competing financial interests.

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Supplementary Figures 1–3 and Supplementary Tables 1 and 2 (PDF 168 kb)

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Kim, H., Huang, J. & Chen, J. CCDC98 is a BRCA1-BRCT domain–binding protein involved in the DNA damage response. Nat Struct Mol Biol 14, 710–715 (2007). https://doi.org/10.1038/nsmb1277

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