Germ-line mutations of the BRCA2 tumor suppressor gene greatly increase the risk of developing breast and ovarian cancers. Here, we show that wild-type BRCA2, but not a tumor-specific truncated mutant BRCA2, synergizes with the nuclear receptor coactivator p160 GRIP1 to enhance transcriptional activation by androgen receptor (AR). BRCA2 not only associates with AR and GRIP1 but also cooperates ...

The breast cancer susceptibility gene, BRCA1, was isolated in 1994. Recent investigations into the genetic epidemiology of BRCA1 have revealed an unexpectedly high prevalence of mutations amongst Ashkenazi Jews. Analyses of BRCA1 function have indicated that it may act as an inhibitor of cell proliferation and is necessary for normal development in the mouse. The presence of a motif in BRCA1 ch...

In modern molecular genetics, epistasis analysis is a tool for probing the relationship between two genes and, hence, between the two genes’ products. In its broadest sense, an epistatic relationship exists when combinations of specific alleles of two or more genes generate a quantitative phenotype that differs from the simple addition of phenotypes associated with each individual allele. Many ...

The breast cancer susceptibility gene BRCA2 has been suggested to function as a "caretaker" of the genome. Cells without wild-type BRCA2 are deficient in repairing DNA damage. However, whether BRCA2 can also suppress oncogenesis by regulating cell proliferation remains to be determined. To address this question, the expression of wild-type BRCA2 protein was reconstituted, in an either constitut...

BRCA2, a gene responsible for inherited susceptibility to breast cancer in a number of families, is thought to be critical for replication and repair of DNA during S-phase. To elucidate the physiological functions of BRCA2, we used a yeast two-hybrid system to screen for proteins that could associate with BRCA2. Here we report interaction of BRCA2 with a mitotic checkpoint protein, hBUBR1, and ...

It has been suggested that BRCA2, the protein product of the breast cancer susceptibility gene BRCA2, is involved in DNA damage repair. It is therefore likely that BRCA2 plays a role in a signaling pathway induced by DNA-damaging agents. To test this possibility, we examined the alteration of the BRCA2 protein level in human cell lines after UV irradiation. We found that UV irradiation down-reg...

BRCA1, BRCA2, and PALB2 are key players in cellular tolerance to chemotherapeutic agents, including camptothecin, cisplatin, and PARP inhibitor. The N-terminal segment of BRCA2 interacts with PALB2, thus contributing to the formation of the BRCA1-PALB2-BRCA2 complex. To understand the role played by BRCA2 in this complex, we deleted its N-terminal segment and generated BRCA2(Δ)(N) mutant cells....

JF305 is a highly prolific pancreatic cancer cell line that originated from a Chinese patient. The cell line bears a functional HR double strand DNA repair mechanism but very responsive to PARP treatment a phenomenon clearly suggesting presence of an anomaly in the mechanism. Brca1, Brca2 and CHK2 proteins are very important constituents of the HR mechanism whose respective gene coding mutation...

The positional cloning of a familial tumor suppressor gene is a monumental task often involving the coordinated efforts of international consortia of many laboratories. The euphoria that accompanies the successful cloning of a cancer-causing gene signals the initiation of many new avenues of study that attempt to define the activity of that gene’s product. These goals are laudatory, because by ...

Cloning of a breast cancer-predisposing gene (BRCA2) on chromosome 13q12-14 has been reported recently. We analyzed seven large Icelandic breast cancer families with markers from the BRCA2 region. Five families showed strong evidence of linkage. The maximum twopoint LOD scores for the five BRCA2-linked families ranged from 1.06 to 3.19. Haplotype analyses revealed a region with identical allele...