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Science 316 (5828): 1202-1205

Copyright © 2007 by the American Association for the Advancement of Science

Ubiquitin-Binding Protein RAP80 Mediates BRCA1-Dependent DNA Damage Response

Hongtae Kim,1 Junjie Chen,1* Xiaochun Yu2*

Abstract: Mutations in the breast cancer susceptibility gene 1 (BRCA1) are associated with an increased risk of breast and ovarian cancers. BRCA1 participates in the cellular DNA damage response. We report the identification of receptor-associated protein 80 (RAP80) as a BRCA1-interacting protein in humans. RAP80 contains a tandem ubiquitin-interacting motif domain, which is required for its binding with ubiquitin in vitro and its damage-induced foci formation in vivo. Moreover, RAP80 specifically recruits BRCA1 to DNA damage sites and functions with BRCA1 in G2/M checkpoint control. Together, these results suggest the existence of a ubiquitination-dependent signaling pathway involved in the DNA damage response.

1 Department of Therapeutic Radiology, Yale University School of Medicine, Post Office Box 208040, New Haven, CT 06520, USA.
2 Division of Molecular Medicine and Genetics, Department of Internal Medicine, University of Michigan Medical School, 109 Zina Pitcher Place, 1520 Biomedical Science Research Building, Ann Arbor, MI 48109, USA.

* To whom correspondence should be addressed. E-mail: Junjie.chen{at}yale.edu (J.C.); xiayu{at}med.umich.edu (X.Y.)

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