The BRCA1 protein specifically enhances the global genomic repair pathway and induces DNA repair gene expression.
Mutations in the BRCA1 gene are associated with increased risk of breast cancer and are often accompanied by mutation of the p53 tumor suppressor gene product. In an Advanced Online Publication in Nature Genetics, Anne-Renee Hartman and James Ford from the Stanford University Medical Center in California, describe a role for the BRCA1 protein in regulating DNA-repair pathways (Nat Genet 2002, DOI:10.1038/ng953).
Hartman and Ford constructed human cell lines with a tetracycline-regulated BRCA1 allele, in the presence or absence of functional p53. Overexpression of BRCA1 led to increased global genomic repair, a subtype of nucleotide-excision repair. BRCA1 induced expression of genes known to be involved in nucleotide-excision repair, such as GADD45, XPC and DDB2, in the p53-deficient cells. They suggest that BRCA1 plays an important role in DNA repair and maintaining genome stability, and regulates a key early step in a process of multi-stage tumor progression.
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