Although the BRCA1 tumor suppressor has been implicated in many cellular processes, the biochemical mechanisms by which it influences these diverse pathways are poorly understood. The only known enzymatic function of BRCA1 is the E3 ubiquitin ligase activity mediated by its highly conserved RING domain. In vivo, BRCA1 associates with the BARD1 polypeptide to form a heterodimeric BRCA1/BARD1 com...

BRCA1 is a checkpoint and DNA damage repair gene that secures genome integrity. We have previously shown that mice lacking full-length Brca1 (Brca1(delta11/delta11)) die during embryonic development. Haploid loss of p53 completely rescues embryonic lethality, and adult Brca1(delta11/delta11)p53+/- mice display cancer susceptibility and premature aging. Here, we show that reduced expression and/...

BRCA1, a tumor suppressor gene, is implicated in the repression and activation of transcription via interactions with a diverse range of proteins. The mechanisms regulating the action of BRCA1 are not fully understood. Here, we use the promoters of Gadd45alpha, p27(KIP1) and p21(WAF1/CIP1) to demonstrate that SUMO1 represses transactivation potential of BRCA1 by causing BRCA1 to be released fro...

Women who carry a germline mutation in BRCA1 gene typically develop triple negative breast cancers (TNBC) and high grade serous ovarian cancers (HGSOC). Previously, we reported that wild type BRCA1 proteins, unlike the disease-associated mutant BRCA1 proteins to bind the sole sumo E2-conjugating enzyme Ubc9. In this study, we have used clinically relevant cell lines with known BRCA1 mutations a...

Mutations in the breast cancer susceptibility gene 1 (BRCA1) may account for one half of all familial breast cancers. Because of the wide spectrum of different germline mutations, identification of BRCA1 mutation carriers using current techniques is laborious and difficult. The majority of the identified mutations, however, lead to aberrant expression of the gene product in tumor tissue, potent...

Breast cancer, early onset 1 (BRCA1) encodes a nuclear protein that participates in breast and ovarian cancer suppression. The molecular basis for the gender and tissue specificity of the BRCA1 cancer syndrome is unknown. Recently, we observed that a fraction of BRCA1 in female cells is localized on the inactive X chromosome (Xi). Chromatin immunoprecipitation (ChIP) experiments have demonstrat...

The BRCA1 gene on human chromosome 17q21 is responsible for an autosomal dominant syndrome of inherited early onset breast/ovarian cancer. It is estimated that women harboring a germline BRCA1 mutation incur an 85% lifetime risk of breast cancer and a greatly elevated risk of ovarian cancer. The BRCA1 gene has recently been isolated and mutations have been found in the germline of affected indi...

BRCA1 (Breast Cancer 1) has been implicated in a number of cellular processes, including transcription regulation, DNA damage repair and protein ubiquitination. We previously demonstrated that BRCA1 interacts with PABP1 (Poly(A)-Binding Protein 1) and that BRCA1 modulates protein synthesis through this interaction. To identify the mRNAs that are translationally regulated by BRCA1, we used a mic...

We have evaluated the role played by BRCA1 in mediating the phenotypic response to a range of chemotherapeutic agents commonly used in cancer treatment. Here we provide evidence that BRCA1 functions as a differential mediator of chemotherapy-induced apoptosis. Specifically, we demonstrate that BRCA1 mediates sensitivity to apoptosis induced by antimicrotubule agents but conversely induces resis...

The breast cancer susceptibility gene 1 (BRCA1) has been shown to maintain genomic stability through multiple functions in the regulation of DNA damage repair and transcription. Its translated BRCT (BRCA1 C-terminal domain) acts as a strong transcriptional activator. BRCA1 damaged by carboplatin treatment may lead to a loss of such functions. To address the possibility of the BRCA1 gene as a th...