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Papers In Press, published online ahead of print August 14, 2001
J. Biol. Chem, 10.1074/jbc.M105227200
Submitted on June 6, 2001
Revised on August 14, 2001
Accepted on August 14, 2001

Redistribution of BRCA1 among four different protein complexes following replication blockage

Natsuko Chiba and Jeffrey D. Parvin

Pathology, Brigham and Women's Hospital, Boston, MA 02115

Corresponding Author: jparvin{at}rics.bwh.harvard.edu

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 which has not been described previously. We observed this new complex after treating cells with hydroxyurea (HU), suggesting that the HUIC (hydroxyurea induced complex) is involved with the response to DNA replication blockage. Following HU 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 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 following DNA replication blockage.


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