Poly(ADP-ribose) polymerase (PARP) inhibitors have been proven to represent superior clinical agents targeting DNA repair mechanisms in cancer therapy. We investigated PARP inhibitory effects of the natural and synthetic flavonoids (quercetin, rutin, monoglucosyl rutin and maltooligosyl rutin) and tested the synthetic lethality in BRCA2 mutated cells. In vitro ELISA assay suggested that the fla...

We recently published a new scoring system to estimate the chance of identifying mutations in the BRCA1 and BRCA2 genes (table 1). A potential criticism of the original paper was that not all cases were fully screened for mutations in both BRCA1 and BRCA2. We have now extended our analyses to address this. In total, we have screened 921 samples from familial breast cancer pedigrees from the Man...

Overexpression of the Aurora A kinase has been shown to have prognostic value in breast cancer. Previously, we showed a significant association between AURKA gene amplification and BRCA2 mutation in breast cancer. The aim of this study was to assess the prognostic impact of Aurora A overexpression on breast cancer arising in BRCA2 mutation carriers. Aurora A expression was evaluated by immunohi...

Biallelic mutations in the human breast cancer susceptibility gene, BRCA2, are associated with Fanconi anemia, implying that some persons who inherit 2 deleterious variants of BRCA2 are able to survive even though it is well established that BRCA2 is indispensable for viability in mice. One such variant, IVS7 + 2T > G, results in premature protein truncation because of skipping of exon 7. Surpr...

The breast cancer susceptibility gene BRCA2 is expressed in a wide range of tissues as an 11-kb mRNA transcript encoding a 3418-amino acid protein, which is involved in the response to DNA damage. To obtain a better molecular characterization of BRCA2 expression in breast tissue, we analyzed full-length BRCA2 mRNA by means of reverse transcriptase-PCR with a panel of primer pairs encompassing t...

A rare hereditary disorder, Fanconi anemia (FA), is caused by mutations in an array of genes, which interact in a common FA pathway/network. These genes encode components of the FA "core" complex, a key factor FancD2, the familial breast cancer suppressor BRCA2/FancD1, and Brip1/FancJ helicase. Although BRCA2 is known to play a pivotal role in homologous recombination repair by regulating Rad51...

Mild mutations in BRCA2 (FANCD1) cause Fanconi anemia (FA) when homozygous, while severe mutations cause common cancers including breast, ovarian, and prostate cancers when heterozygous. Here we report a zebrafish brca2 insertional mutant that shares phenotypes with human patients and identifies a novel brca2 function in oogenesis. Experiments showed that mutant embryos and mutant cells in cult...

Two BRCA2-like sequences are present in the Arabidopsis genome. Both genes are expressed in flower buds and encode nearly identical proteins, which contain four BRC motifs. In a yeast two-hybrid assay, the Arabidopsis Brca2 proteins interact with Rad51 and Dmc1. RNAi constructs aimed at silencing the BRCA2 genes at meiosis triggered a reproducible sterility phenotype, which was associated with ...

The breast cancer susceptibility gene BRCA2 encodes a protein of 3418 amino acids which does not exhibit substantial sequence similarity to any other protein in the public databases. A dot matrix comparison of BRCA2 with itself revealed an eight times repeated motif in the segment of the protein encoded by exon 11. As a preliminary test of the hypothesis that these motifs are functionally signi...

BACKGROUND A C/T transition - rs4987117 (the Thr1915Met polymorphism) and an A/G transition - rs11571653 (the Met784Val polymorphism) in the BRCA2 gene were linked to breast cancer risk in Polish and Japanese populations, respectively. AIM To study the association between polymorphisms of the BRCA2 gene and clinical parameters in breast cancer. METHODS Both polymorphisms were evaluated by R...