Genetic instability in the RAD51 and BRCA1 regions in breast cancer

Abstract

Abbreviations used: AML -acute myeloid leukemia; BACH1 helicase -BRCA1 interacting protein C-terminal helicase 1 [Homo sapiens]; BRCA1 -breast cancer susceptibility gene 1; BRCT -BRCA C-terminus; LOH -loss of heterozygosity; RecA -RecA protein (Recombinase A); MRE11 -meiotic recombination 11 homologue A; NBS1 -Nijmegen breakage syndrome 1 (nibrin, NBN); p53 -tumor protein 53; RAD50 -RAD50 homologue (Saccharomyces cerevisiae) [ Abstract: Breast cancer is the most prevalent cancer type in women. Accumulating evidence indicates that the fidelity of double-strand break repair in response to DNA damage is an important step in mammary neoplasias. The RAD51 and BRCA1 proteins are involved in the repair of double-strand DNA breaks by homologous recombination. In this study, we evaluated loss of heterozygosity (LOH) in the RAD51 and BRCA1 regions, and their association with breast cancer. The polymorphic markers D15S118, D15S214 and D15S1006 were the focus for RAD51, and D17S855 and D17S1323 for BRCA1. Genomic deletion detected by allelic loss varied according to the regions tested, and ranged from 29 to 46% of informative cases for the RAD51 region and from 38 to 42% of informative cases for the BRCA1 region. 25% of breast cancer cases displayed LOH for at least one studied marker in the RAD51 region exclusively. On the other hand, 31% of breast cancer cases manifested LOH for at least one microsatellite marker concomitantly in the RAD51 and BRCA1 regions. LOH in the RAD51 region,

The level of oxidative stress and the expression of genes involved in DNA-damage signaling pathways in depressive patients with colorectal carcinoma

“…Rad51, a homolog of Escherichia coli RecA, is a DNA-dependent ATPase that binds cooperatively to single-stranded DNA to form a nucleoprotein filament that functions in the strandinvasion step of homologous recombination [39], which repairs chromosome damage and is indispensable for tumor suppression in humans. Recent studies have suggested that RAD51-associated protein 1 promotes homologous recombination and genomic stability by enhancing RAD51 recombinase [40]. XRCC3 is homologous to Rad51 and is essential for repairing double-strand DNA breaks by homologous recombination between sister chromatids [41].…”

The role of polyphenols in overcoming cancer drug resistance: a comprehensive review

“…This implies that curcumin-induced enhanced cisplatin sensitivity is mediated by suppression of the FA/BRCA pathway [ 167 ]. BRCA1 and RAD51 are two proteins leading to homologous recombination (HR) and thereby repair of double-strand DNA breaks [ 168 ].…”

Role of Rad51 and DNA repair in cancer: A molecular perspective

“…In terms of somatic RAD51 mutations in tumor tissues, one study reported LOH of this gene -located on chromosome 15q14-15 -in 41 out of 127 BC patients (Gonzalez et al, 1999). Along this line, Nowacka-Zawisza et al evaluated LOH in RAD51 and its association with BC by analyzing the recombinase polymorphic markers D15S118, D15S214, and D15S1006 (Nowacka-Zawisza, Brys, Romanowicz-Makowska, Kulig, & Krajewska, 2007). Genomic deletion detected by allelic loss ranged from 29 to 46% of informative cases for the RAD51 region, 25% of the analyzed BCs displayed LOH for at least one RAD51 marker, and LOH in RAD51 appeared to correlate with the steroid receptor status, suggesting a role for enhanced risk in BC development.…”