Breast cancer gene 1 (BRCA1): role in cell cycle regulation and DNA repair-perhaps through transcription

Abstract

Mutations of BRCA1 gene are associated with more than half the cases of hereditary breast cancer. Breast cancer formation in BRCA1 mutation carriers is generally accompanied by loss of the wild-type allele, suggesting that BRCA1 protein may function as a tumor suppressor. The human BRCA1 gene encodes a nuclear protein of 1863 amino acids. Although several lines of evidences suggest that BRCA1 protein may have a role to play in cell cycle regulation, DNA repair, and other processes, the exact mechanism of functioning by BRCA1 protein is not clear. Recent evidences from several laboratories suggest that BRCA1 may regulate the expression of many genes like p21^WAF1/CIP1, Gadd45, Cyclin B1, DBB2, XPC, 14-3-3ó and others at the level of transcription. These BRCA1-regulated gene products have been implicated directly or indirectly in cell cycle regulation and DNA repair. Thus a plausible model is proposed in which BRCA1 protein may bring its effects on cell cycle and DNA repair through its ability to modulate gene expression at the level of transcription.