Accession Number : ADA487025


Title :   Regulation of BRCA1 Function by DNA Damage-Induced Site-Specific Phosphorylation


Descriptive Note : Annual summary rept. 15 May 2002-15 May 2007


Corporate Author : UNIVERSITY OF NORTH TEXAS HEALTH SCIENCE CENTER FORT WORTH TX


Personal Author(s) : Boyer, Thomas G


Full Text : https://apps.dtic.mil/dtic/tr/fulltext/u2/a487025.pdf


Report Date : Jun 2007


Pagination or Media Count : 87


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.


Descriptors :   *FIBROBLASTS , *BREAST CANCER , *PHOSPHORYLATION , *TRANSCRIPTION(GENETICS) , *DEOXYRIBONUCLEIC ACIDS , SIGNALS , OVARIES , GENETICS , REPAIR , CULTURES(BIOLOGY) , EFFICIENCY , NEOPLASMS , TOOLS


Subject Categories : Biochemistry
      Genetic Engineering and Molecular Biology
      Medicine and Medical Research


Distribution Statement : APPROVED FOR PUBLIC RELEASE