The Function of BRCA1 in DNA Damage Response

Abstract

Affecting approximately one in nine women during their life time, breast cancer is one of the most common causes of cancer and cancer-related mortality in women (Alberg and Helzlsouer 1997;Paterson 1998). Although most breast cancers are sporadic, 5-10% of breast cancers are heritable. Germ-line mutations in the BRCA1 gene are found in almost all of the families with inherited breast and ovarian cancers and about half of the families with only breast cancer (Easton et al. 1993; for review, see Feunteun and Lenoir 1996). Because loss of heterozygosity is detected in the BRCA1 gene in cancer cells from BRCA1 mutation carriers, BRCA1 is considered to be a tumor suppressor (Smith et al. 1992). Although evidence indicates that BRCA1 is involved in maintaining genome integrity, the biochemical functions of BRCA1 and how the BRCA1 mutations contribute to cancer development are poorly understood. In this paper, we focus on how the presence of DNA damage is transmitted to BRCA1 and speculate on how BRCA1 functions as a tumor suppressor. For a more general overview of BRCA1 function(s) and its role as a tumor suppressor, see one of the excellent reviews published recently (Chen et al.