Heritable mutations in the BRCA1 and BRCA2 and other genes in the DNA double-strand break (DSB) repair pathway disrupt binding of the encoded proteins, transport into the nucleus and initiation of homologous recombination, thereby increasing cancer risk [Scully, R., Chen, J., Plug, A., Xiao, Y., Weaver, D., Feunteun, J., Ashley, T. and Livingston, D.M. (1997) Association of BRCA1 with Rad51 in ...

BACKGROUND The frequency of BRCA1 germline mutations among Chinese women with triple-negative breast cancer is unclear, and the association between BRCA1 mutations and the response to neoadjuvant chemotherapy in women with triple-negative breast cancer has not been determined. PATIENTS AND METHODS Nine hundred and fifty-six triple-negative breast cancer patients were treated at our institute ...

Studies have showed that dysfunction in the breast cancer susceptibility gene (BRCA) is associated with triple-negative breast cancer (TNBC); however, its effect on patient survival remains controversial. We investigated the distribution of BRCA1/2 mutations in unselected Chinese patients with TNBC and explored their roles in prognosis. Then a systematic review and meta-analysis were performed ...

BRCA1 and BRCA2 are prominently associated with inherited breast and ovarian cancer. The encoded proteins function in DNA damage responses, but no functional link between BRCA1 and BRCA2 has been established. We show here that PALB2 physically and functionally connects BRCA1 and BRCA2 into a DNA damage response network that also includes the RAD51 recombinase. PALB2 directly binds BRCA1, as det...

BRCA1 localizes to discrete nuclear foci (dots) during S phase. Hydroxyurea-mediated DNA synthesis arrest of S phase MCF7 cells led to a loss of BRCA1 from these structures. Ultraviolet light, mitomycin C, or gamma irradiation produced a similar effect but with no concurrent arrest of DNA synthesis. BARD1 and Rad51, two proteins associated with the BRCA1 dots, behaved similarly. Loss of the BRC...

The breast cancer suppressor BRCA1 forms a stable heterodimeric E3 ubiquitin ligase with BARD1. Each protein controls the abundance and stability of the other, and loss of the interaction leads to BRCA1 degradation. Here, we show that HERC2, a protein recently implicated in DNA damage repair, targets BARD1-uncoupled BRCA1 for degradation. HERC2 shuttles between the nucleus and the cytoplasm. It...

The breast cancer susceptibility gene 1 (BRCA1) and glutathione S-transferase P1 (GSTP1) promoters are reportedly often methylated in breast cancer tissues. Their methylation status in surrounding normal breast tissues has not been examined thoroughly although this may well be important for a better understanding of breast carcinogenesis. In this study, BRCA1 and GSTP1 promoter methylation was ...

BRCA1, a breast and ovarian cancer susceptibility gene, has been implicated in gene regulation. Previous studies demonstrate that BRCA1 induces GADD45, a p53-regulated and stress-inducible gene that plays an important role in cellular response to DNA damage. However, the mechanism(s) by which BRCA1 regulates GADD45 remains unclear. In this report, we have shown that BRCA1 activation of the GADD...

A role for BRCA1 in the direct and indirect regulation of transcription is well established. However, a comprehensive view of the degree to which BRCA1 impacts transcriptional regulation on a genome-wide level has not been defined. We performed genome-wide expression profiling and ChIP-chip analysis, comparison of which revealed that although BRCA1 depletion results in transcriptional changes i...

PURPOSE Pancreatic ductal adenocarcinoma (PDAC) is associated with the breast ovarian cancer syndrome (BRCA1/BRCA2) mutations. It is unknown if this association is causal. EXPERIMENTAL DESIGN This is a single-site study of patients who underwent surgical pancreatic tumor resection and self-identified as Ashkenazi Jewish. DNA from normal pancreatic tissue was genotyped for the three Ashkenazi ...