The tumor suppressor protein BRCA1 localizes to sites of DNA double-strand breaks (DSB), promoting repair by homologous recombination through the recruitment of DNA damage repair proteins. In normal cells, homologous recombination largely depends on BRCA1. However, assembly of the pivotal homologous recombination regulator RAD51 can occur independently of BRCA1 in the absence of 53BP1, another ...

The Polycomb-repressive complex 2 (PRC2) is important for maintenance of stem cell pluripotency and suppression of cell differentiation by promoting histone H3 lysine 27 trimethylation (H3K27me3) and transcriptional repression of differentiation genes. Here we show that the tumour-suppressor protein BRCA1 interacts with the Polycomb protein EZH2 in mouse embryonic stem (ES) and human breast can...

Cancer cells afflicted with mutations in the breast cancer susceptibility protein (BRCA1) often suffer from increased DNA damage and genomic instability. The precise manner in which physical changes to BRCA1 influence its role in DNA maintenance remains unclear. We used single-particle electron microscopy to study the three-dimensional properties of BRCA1 naturally produced in breast cancer cel...

BRCA1 is a large multi-domain protein with a pivotal role in maintaining genome stability and cell cycle progression. Germline mutations in the BRCA1 gene confer an estimated lifetime risk of 60%-80% for breast cancer and 15%-60% for ovarian cancer. Many of the germline mutations associated with cancer development are concentrated in the amino terminal RING domain and the carboxyl terminal BRCT...

Glioblastomas (GBMs) are one of the most malignant brain tumors in adults. This is partly due to potential presence so-called glioma stem-like cells (GSCs), which characterized by expression stemness markers and a resistance radio- chemotherapy. Previous work from us showed that after combination treatment GSCs with arsenic trioxide gossypol, protein BRCA1-associated ATM-activator 1 (BRAT1) was...

Breast cancer 1 (BRCA1), as a tumor suppressor, exerts an effective influence on protecting DNA integrity to suppress the development of breast cancer (BC). BRCA1 expression is induced in response to DNA-damaging agents such as etoposide. Germline BRCA1 gene mutations are associated with development of hereditary BC. However, besides BRCA-mutated BCs, some sporadic cancers may also exhibit a BR...

Heterochromatin protein 1γ (HP1γ) is a chromatin protein involved in gene silencing. Herein, we show that HP1γ interacts with breast cancer type 1 susceptibility protein (BRCA1) and regulates BRCA1-mediated transcription via modulation of promoter occupancy and histone modification. We used several HP1γ mutants and small interfering RNAs for histone methyltransferases to show that BRCA1-HP1γ in...

BRCA1 is a breast and ovarian cancer-specific tumor suppressor that seems to be involved in transcription and DNA repair. Here we report that BRCA1 exhibits a bona fide ubiquitin (Ub) protein ligase (E3) activity, and that cancer-predisposing mutations within the BRCA1 RING domain abolish its Ub ligase activity. Furthermore, these mutants are unable to reverse gamma-radiation hypersensitivity o...