Characterization of S-Phase Specific BRCA1-Containing Complex
Annual summary rept. 1 Jun 2000-30 May 2003
BRIGHAM AND WOMEN'S HOSPITAL BOSTON MA
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This study will fully characterize the function of a BRCA1 containing protein complex, which appears in cells following DNA replication arrest using hydroxyurea. The complex, originally referred to as the S-phase specific complex and now termed the Hydroxyurea Induced Complex HUIC, was observed in HeLa and in 293 cells. Hydroxyurea treatment of cells results in the reduction of BRCA1 content in the RNA polymerase II holoenzyme complex with a complementary increase in the HUIC. We have begun to characterize both complexes, and we find that the HUIC does not contain the repair proteins RAD50MRE11NBS1 as originally surmised, but does contain BRCA1 and the BARD1 polypeptides. We model that the HUIC results from the proteolytic degradation of the RNA polymerase II holoenzyme following DNA damage. Work is continuing to identify the polypeptides which compose the HUIC and to determine its role in breast cancer.
- Genetic Engineering and Molecular Biology
- Medicine and Medical Research