Tandem breast cancer C-terminal (BRCT) domains, present in many DNA repair and cell cycle checkpoint signaling proteins, are phosphoprotein binding modules. The best-characterized tandem BRCT domains to date are from the protein BRCA1 (BRCA1-BRCT), an E3 ubiquitin ligase that has been linked to breast and ovarian cancer. While X-ray crystallography and NMR spectroscopy studies have uncovered th...

Both human and mouse cells express an alternatively spliced variant of BRCA1, BRCA1-Delta11, which lacks exon 11 in its entirety, including putative nuclear localization signals. Consistent with this, BRCA1-Delta11 has been reported to reside in the cytoplasm, a localization that would ostensibly preclude it from playing a role in the nuclear processes in which its full-length counterpart has b...

Cells deficient in the Werner syndrome protein (WRN) or BRCA1 are hypersensitive to DNA interstrand cross-links (ICLs), whose repair requires nucleotide excision repair (NER) and homologous recombination (HR). However, the roles of WRN and BRCA1 in the repair of DNA ICLs are not understood and the molecular mechanisms of ICL repair at the processing stage have not yet been established. This stu...

The breast cancer 1 (BRCA1) protein is a tumor suppressor playing roles in DNA repair and cell cycle regulation. Studies of DNA repair functions of BRCA1 have focused on double-strand break (DSB) repair pathways and have recently included base excision repair (BER). However, the function of BRCA1 in BER is not well defined. Here, we examined a BRCA1 role in BER, first in relation to alkylating ...

T he BRCA1 gene was cloned in 1994 as the first tumor suppressor of hereditary breast cancer, and it has been heavily studied ever since. The Brca1 protein is multifunctional and critical for the maintenance of genomic stability. Among its many roles, Brca1 is part of an E3 ubiquitin ligase important for homologous recombination (HR) and signaling of double-strand DNA breaks (DSBs). In response...

The breast cancer susceptibility gene BRCA1 encodes a large protein thought to contribute to a variety of cellular processes, although the critical determinants of BRCA1-deficient tumorigenesis remain unclear. Given that BRCA1 is required for cell proliferation, suppressor mutations are believed to modify BRCA1 phenotypes and contribute to the etiology of BRCA1-deficient tumors. Here, we show t...

This study investigated whether prepubertal dietary exposure to genistein reduces mammary tumorigenesis by upregulating Brca1 expression in mice. Heterozygous Brca1(+/-) mice and their wild-type (WT) littermates were fed control AIN93G diet or 500 ppm genistein-supplemented AIN93G diet from postnatal day (PND) 15 to PND30 and then switched to AIN93G diet. Prepubertal dietary exposure to geniste...

The BRCA1 gene was identified and cloned in 1994 based on its linkage to early onset breast and ovarian cancer syndromes in women. The tumor suppressor, BRCA1 is known as a major player in the DNA damage response. These are evident from its loss, which causes malignant transformation in breast and ovary, and renders cells to become sensitive to a wide variety of DNA damaging agents. Here, we ha...

The breast and ovarian cancer susceptibility gene-1 (BRCA1) located on chromosome 17q21 encodes a tumor suppressor gene that functions, in part, as a caretaker gene in preserving chromosomal stability. The observation that most BRCA1 mutant breast cancers are hormone receptor negative has led some to question whether hormonal factors contribute to the etiology of BRCA1-mutant breast cancers. Ne...

Mutations in the breast cancer susceptibility gene 1 (BRCA1) account for a substantial percentage of familial breast and ovarian cancers. Although BRCA1 is thought to function within the nucleus, it has also been located in the cytoplasm. In addition, BRCA1 accumulates in the nucleus of cells treated with leptomycin B, an inhibitor of chromosome region maintenance 1-mediated nuclear export, ind...