Regulation of BRCA1 Function by DNA Damage-Induced Site-Specific Phosphorylation
Abstract
BRCA1, a hereditary breast and ovarian specific tumor suppressor, ensures genomic integrity through its control of transcription and repair of damaged DNA. Considerable evidence implicates DNA damage-induced site-specific phosphorylation in the modulation of its biological activity. However, it is not presently clear whether and how the transcription and DNA repair activities of BRCA1 are modulated in response to DNA damage signals. We have engineered and refined a unique combination of biochemical and genetic tools to address this issue. First, we have developed a biochemical means by which to resolve BRCA1-containing complexes involved in transcription from those involved in DNA double-strand break repair. This should render it feasible to identify DNA damage-induced site-specific phosphorylation events with potential functional relevance to the role of BRCA1 in these two processes. Second, we have established fibroblast cultures from brca1-deficient mouse embryos and developed BRCA1-dependent transcription and repair assays based on the use of these cells. This system will expedite the facile and efficient analysis of the effects of targeted BRCA1 mutations at identified or predicted sites of phosphorylation on its transcription and DNA repair activities. Collectively, these studies should illuminate the molecular basis for the caretaker properties of BRCA1.
Document Details
- Document Type
- Technical Report
- Publication Date
- May 01, 2002
- Accession Number
- ADA406148
Entities
People
- Thomas G. Boyer
Organizations
- University of Texas Health Science Center at San Antonio