Cell Cycle Analysis of the BRCA1 Gene Product
Abstract
This project is focused upon a functional analysis of BRCA1, the hereditary breast/ovarian cancer susceptibility gene. Our aims were to identify proteins that interact with BRCA1 and to determine the functional significance of such interactions. To this end, we discovered that BRCA1 interacts with the product of the second major hereditary breast/ovarian cancer gene, BRCA2. Each of these proteins interacts with the recombination protein, Rad51, suggesting a role for BRCA1 and BRCA2 in double strand break repair (DSBR). We developed a functional assay capable of distinguishing between wild-type and mutant alleles of BRCA1. Wild-type but not mutant alleles of BRCA1 were able to restore efficient DSBR to a BRCA1 -/- cell line, HCC1937. Finally, we cloned a novel helicase, termed BACH1, that interacts specifically and directly with the BRCT motifs of BRCA1. Our data suggest that the interaction of BRCA1 with BACH1 is required for efficient DSBR, and that mutation of BACH1 may contribute to human breast cancer susceptibilty.
Document Details
- Document Type
- Technical Report
- Publication Date
- Sep 01, 2000
- Accession Number
- ADA405841
Entities
People
- Dennis M. Lynch
Organizations
- Dana–Farber Cancer Institute