Regulatory Mechanisms in Transcriptional Activation by BRCA1
Abstract
The long-range goal of the laboratory is to elucidate the role of genes involved in the development of breast and ovarian cancer, with a focus on the function of the tumor suppressor gene BRCAl. The human BRCAl gene codes for a nuclear phosphoprotein that is likely to be multifunctional. Recent genetic and biochemical evidence indicates that BRCAl participates in the cellular DNA damage response. However, it is not known how BRCAl exert its actions. Several lines of evidence suggest that it may function through transcription. Our working model is that impairment of BRCAl-mediated transcription activation predisposes to the development of cancer. By the end of the third year of our project we were able to develop a functional assay system to study the impact of all unclassified missense variants of BRCAl that are located between aa 1366 and 1864 greatly expanding the scope of the transcription assay. In the course of this work we have also identified mutations in exon 13 that affect transcription activation and may define a region important for transcriptional regulation. Our results, taken together, reinforce the notion that sequences coded by exons 12 and 13 are important for the regulation of transcription by BRCAl.
Document Details
- Document Type
- Technical Report
- Publication Date
- May 01, 2002
- Accession Number
- ADA405483
Entities
People
- Alvaro Monteiro