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Originally published In Press as doi:10.1074/jbc.M105227200 on August 14, 2001

J. Biol. Chem., Vol. 276, Issue 42, 38549-38554, October 19, 2001
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Redistribution of BRCA1 among Four Different Protein Complexes following Replication Blockage*

Natsuko Chiba and Jeffrey D. ParvinDagger

From the Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115

The BRCA1 protein is known to participate in multiple cellular processes. In these experiments, we resolved four distinct BRCA1-containing complexes. We found BRCA1 associated with the RNA polymerase II holoenzyme (holo-pol), a large mass complex called the fraction 5 complex, the Rad50-Mre11-Nbs1 complex, and a complex that has not been described previously. We observed this new complex after treating cells with hydroxyurea, suggesting that the hydroxyurea-induced complex (HUIC) is involved with the response to DNA replication blockage. After hydroxyurea treatment of cells, BRCA1 content decreased in the holo-pol and the fraction 5 complex, and BRCA1 was redistributed to the HUIC. The HUIC was shown not to contain a number of holo-pol components or the Rad50-Mre11-Nbs1 complex but was associated with the BRCA1-associated RING domain protein BARD1. These data suggest that BRCA1 participates in multiple cellular processes by multiple protein complexes and that the BRCA1 content of these complexes is dynamically altered after DNA replication blockage.

* This work was supported by Fellowship DAMD17-00-1-0164 from the United States Army Medical Research and Materiel Command (to N. C.), Grant RPG-99-097-01 from the American Cancer Society, and pilot grants from the Elsa U. Pardee Foundation and The Concert for the Cure (to J. D. P.).The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

Dagger To whom correspondence should be addressed: Dept. of Pathology, Brigham and Women's Hospital, 75 Francis St., Boston, MA 02115. Tel.: 617-278-0818; Fax: 617-732-7449; E-mail: jparvin@rics.bwh.harvard.edu.

Copyright © 2001 by The American Society for Biochemistry and Molecular Biology, Inc.


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