The BRCA1-IRIS protein was identified in 2004 [1] and later found to be frequently upregulated in multiple sporadic tumor types, including breast and ovarian cancers [2, 3]. In ovarian cancer samples, BRCA1-IRIS expression increases with tumor progression together with survivin [3]. This trend was positively correlated with significant decrease in the level of total FOXO1 and FOXO3a and increas...

The breast and ovarian cancer predisposition protein BRCA1 forms three mutually exclusive complexes with Fanconi anemia group J protein (FANCJ, also called BACH1 or BRIP1), CtIP, and Abraxas/RAP80 through its BRCA1 C terminus (BRCT) domains, while its RING domain binds to BRCA1-associated RING domain 1 (BARD1). We recently found that the interaction between heterochromatin protein 1 (HP1) and B...

PARP inhibitors have gained recent attention due to their highly selective killing of BRCA1/2-mutated and DNA double-strand break (DSB) repair-deficient tumors. Unfortunately, the majority of sporadic breast cancers carry wild-type BRCA1/2 and are proficient in DSB repair. We and others have shown that BRCA1 is a nuclear/cytoplasm shuttling protein that is transiently exported from the nucleus ...

The BRCA1 tumor suppressor gene is expressed in all mammalian cells. Within these cells, the BRCA1 protein product interacts with several seemingly distinct nuclear complexes. Proteins within these complexes are potential targets for the E3-ubiquitin ligase activity associated with BRCA1:BARD1 complexes. Recent breakthroughs have centered on elucidating critical DNA repair and chromatin-remodel...

A strong candidate for the 17q-linked BRCA1 gene, which influences susceptibility to breast and ovarian cancer, has been identified by positional cloning methods. Probable predisposing mutations have been detected in five of eight kindreds presumed to segregate BRCA1 susceptibility alleles. The mutations include an 11-base pair deletion, a 1-base pair insertion, a stop codon, a missense substit...

The tumor suppressor gene BRCA1 was cloned in 1994 based on its linkage to early-onset breast and ovarian cancer. Although the BRCA1 protein has been implicated in multiple cellular functions, the precise mechanism that determines its tumor suppressor activity is not defined. Currently, the emerging picture is that BRCA1 plays an important role in maintaining genomic integrity by protecting cel...

Individuals carrying a mutation in the breast cancer 1, early onset gene (BRCA1) are at increased risk of breast or ovarian cancer and thus are candidates for risk reduction strategies such as oophorectomy and mastectomy. A recurring problem in the clinic is that many detectable changes within the BRCA1 gene produce subtle alterations to the protein that are not easily recognized as either harm...

Author’s Affi liation: Division of Molecular Pathology, The Netherlands Cancer Institute, Amsterdam, The Netherlands Corresponding Author: Jos Jonkers, Division of Molecular Pathology, The Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands. Phone: 31-20-5122000; Fax: 31-20-5122050; E-mail: [email protected] doi: 10.1158/2159-8290.CD-12-0186 ©2012 American Associati...

The breast cancer suppressor protein, BRCA1, is a ubiquitin ligase expressed in a wide range of tissues. However, inheritance of a single BRCA1 mutation significantly increases a woman’s lifetime chance of developing tissue-specific cancers in the breast and ovaries. Recently, studies have suggested this tissue specificity may be linked to inhibition of estrogen receptor (ER ) transcriptional a...

Breast cancer-associated protein 1 (BRCA1) forms foci at sites of induced DNA damage, but any significance of these normal S-phase foci is unknown. BRCA1 distribution does not simply mirror or overlap that of replicating DNA; however, BRCA1 foci frequently abut sites of BrdU incorporation, mostly at mid-to-late S phase. Although BRCA1 does not overlap XIST RNA across the inactive X chromosome, ...