Search Results: 1 - 10 of 100 matches for " "
All listed articles are free for downloading (OA Articles)
Page 1 /100
Display every page Item
Polimorfizm pojedynczych nukleotydów w genach naprawy DNA przez rekombinacj homologiczn (XRCC2 i RAD51) a ryzyko sporadycznego raka piersi w Polsce  [cached]
Hanna Romanowicz,Beata Smolarz,Jakub Baszczyński,Marek Zadro?ny
Przegl?d Menopauzalny , 2011,
Abstract: Background: Single nucleotide polymorphisms in the DNA repair genes have been extensively studied inassociation with various human cancers such as breast cancer. Material and methods: We investigated an association of polymorphisms in the DNA repair genesXRCC2-Arg188His and RAD51-135G/C with the breast cancer risk. Genotypes were analysed by PCR-RFLP assaysin 80 patients with breast cancer and 80 controls. Results: The distribution of the genotypes of XRCC2 Arg188His in both controls and patients did not differsignificantly (p > 0,05) from those predicted by the Hardy-Weinberg distribution. The C/C genotype of RAD51increased the risk of breast cancer occurrence (OR 2.29; 95% PU (0.91–5.72), p = 0.04). Conclusion: G135C polymorphism of the RAD51 gene may be associated with the incidence of sporadicbreast cancer in Polish women.
Association between the RAD51 135 G>C Polymorphism and Risk of Cancer: A Meta-Analysis of 19,068 Cases and 22,630 Controls  [PDF]
Wei Wang, Jia-Lin Li, Xiao-Feng He, An-Ping Li, Yong-Lin Cai, Na Xu, Shu-Mei Sun, Bing-Yi Wu
PLOS ONE , 2013, DOI: 10.1371/journal.pone.0075153
Abstract: Background RAD51 135G>C can modify promoter activity and the penetrance of BRCA1/2 mutations, which plays vital roles in the etiology of various cancer. To date, previous published data on the association between RAD51 135G>C polymorphism and cancer risk remained controversial. Recent meta-analysis only analyzed RAD51 135G>C polymorphism with breast cancer risk, but the results were also inconsistent. Methods A meta-analysis based on 39 case-control studies was performed to investigate the association between cancer susceptibility and RAD51 135G>C. Odds ratios (OR) with 95% confidence intervals (CIs) were used to assess the association in different inheritance models. Heterogeneity among studies was tested and sensitivity analysis was applied. Results Overall, no significant association was found between RAD51 135G>C polymorphism and cancer susceptibility in any genetic model. In further stratified analysis, significantly elevated breast cancer risk was observed in BRCA2 mutation carriers (recessive model: OR = 4.88, 95% CI = 1.10–21.67; additive model: OR = 4.92, 95% CI = 1.11–21.83). Conclusions This meta-analysis suggests that RAD51 variant 135C homozygote is associated with elevated breast cancer risk among BRCA2 mutation carriers. Moreover, our work also points out the importance of new studies for RAD51 135G>C association in acute myeloid leukemia, especially in Caucasians, where at least some of the covariates responsible for heterogeneity could be controlled, to obtain a more conclusive understanding about the function of the RAD51 135G>C polymorphism in cancer development.
RAD51 and Breast Cancer Susceptibility: No Evidence for Rare Variant Association in the Breast Cancer Family Registry Study  [PDF]
Florence Le Calvez-Kelm, Javier Oliver, Francesca Damiola, Nathalie Forey, Nivonirina Robinot, Geoffroy Durand, Catherine Voegele, Maxime P. Vallée, Graham Byrnes, Breast Cancer Family Registry, John L. Hopper, Melissa C. Southey, Irene L. Andrulis, Esther M. John, Sean V. Tavtigian, Fabienne Lesueur
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0052374
Abstract: Background Although inherited breast cancer has been associated with germline mutations in genes that are functionally involved in the DNA homologous recombination repair (HRR) pathway, including BRCA1, BRCA2, TP53, ATM, BRIP1, CHEK2 and PALB2, about 70% of breast cancer heritability remains unexplained. Because of their critical functions in maintaining genome integrity and already well-established associations with breast cancer susceptibility, it is likely that additional genes involved in the HRR pathway harbor sequence variants associated with increased risk of breast cancer. RAD51 plays a central biological function in DNA repair and despite the fact that rare, likely dysfunctional variants in three of its five paralogs, RAD51C, RAD51D, and XRCC2, have been associated with breast and/or ovarian cancer risk, no population-based case-control mutation screening data are available for the RAD51 gene. We thus postulated that RAD51 could harbor rare germline mutations that confer increased risk of breast cancer. Methodology/Principal Findings We screened the coding exons and proximal splice junction regions of the gene for germline sequence variation in 1,330 early-onset breast cancer cases and 1,123 controls from the Breast Cancer Family Registry, using the same population-based sampling and analytical strategy that we developed for assessment of rare sequence variants in ATM and CHEK2. In total, 12 distinct very rare or private variants were characterized in RAD51, with 10 cases (0.75%) and 9 controls (0.80%) carrying such a variant. Variants were either likely neutral missense substitutions (3), silent substitutions (4) or non-coding substitutions (5) that were predicted to have little effect on efficiency of the splicing machinery. Conclusion Altogether, our data suggest that RAD51 tolerates so little dysfunctional sequence variation that rare variants in the gene contribute little, if anything, to breast cancer susceptibility.
Rad51 Polymerization Reveals a New Chromatin Remodeling Mechanism  [PDF]
Pauline Dupaigne, Christophe Lavelle, Anthony Justome, Sophie Lafosse, Gilles Mirambeau, Marc Lipinski, Olivier Piétrement, Eric Le Cam
PLOS ONE , 2008, DOI: 10.1371/journal.pone.0003643
Abstract: Rad51 protein is a well known protagonist of homologous recombination in eukaryotic cells. Rad51 polymerization on single-stranded DNA and its role in presynaptic filament formation have been extensively documented. Rad51 polymerizes also on double-stranded DNA but the significance of this filament formation remains unclear. We explored the behavior of Saccharomyces cerevisiae Rad51 on dsDNA and the influence of nucleosomes on Rad51 polymerization mechanism to investigate its putative role in chromatin accessibility to recombination machinery. We combined biochemical approaches, transmission electron microscopy (TEM) and atomic force microscopy (AFM) for analysis of the effects of the Rad51 filament on chromatinized templates. Quantitative analyses clearly demonstrated the occurrence of chromatin remodeling during nucleoprotein filament formation. During Rad51 polymerization, recombinase proteins moved all the nucleosomal arrays in front of the progressing filament. This polymerization process had a powerful remodeling effect, as Rad51 destabilized the nucleosomes along considerable stretches of DNA. Similar behavior was observed with RecA. Thus, recombinase polymerization is a powerful mechanism of chromatin remodeling. These remarkable features open up new possibilities for understanding DNA recombination and reveal new types of ATP-dependent chromatin dynamics.
Human Rad51 mediated DNA unwinding is facilitated by conditions that favour Rad51-dsDNA aggregation
Kamakshi Balakrishnan, Neeraja M Krishnan, Anagha Kulkarni, Basuthkar J Rao
BMC Biochemistry , 2009, DOI: 10.1186/1471-2091-10-2
Abstract: We find that human Rad52 (RAD52) stimulates RAD51 mediated DNA unwinding in the presence of all Adenine nucleotide cofactors, (except in AMP and no nucleotide conditions that intrinsically fail to support unwinding reaction) while enhancing aggregation of RAD51-dsDNA complexes in parallel. Interestingly, salt at low concentration can substitute the role of RAD52, in facilitating aggregation of RAD51-dsDNA complexes, that concomitantly also leads to better unwinding.RAD52 itself being a highly aggregated protein perhaps acts as scaffold to bring together RAD51 and DNA molecules into large co-aggregates of RAD52-RAD51-DNA complexes to promote RAD51 mediated DNA unwinding reaction, when appropriate nucleotide cofactors are available, presumably through macromolecular crowding effects. Our work highlights the functional link between aggregation of protein-DNA complexes and DNA unwinding in RAD51 system.RAD51 recombinase, the eukaryotic homolog of RecA, is the core component in homologous recombination (HR). It performs fundamental roles such as homologous pairing and strand exchange in repairing DNA double strand breaks [1,2]. Rad51 binds both ssDNA/dsDNA [3-5] and forms right-handed helical nucleoprotein filaments in which DNA is extended 1.5 times that of B form DNA [4,6-8]. Such extended conformation of DNA in ssDNA-protein filaments is instrumental in facilitating homology search and strand exchange in a three stranded pairing system [8-10]. Even though the equivalent scenario of extended DNA configuration is demonstrable in dsDNA-protein filament, its relevance in HR is not fully understood. However, based on E. coli RecA system, it is surmised that unwinding associated with dsDNA-protein filament is similarly important in four-stranded pairing and strand exchange processes [11]. The first and also most recent report that describes four-stranded exchange reaction catalyzed by RAD51 strongly underscores this aspect where RAD51-dsDNA filament is shown to engage in du
Role of recA/RAD51 family proteins in mammals.  [PDF]
Acta Medica Okayama , 2005,
Abstract: DNA damage causes chromosomal instability leading to oncogenesis, apoptosis, and severe failure of cell functions. The DNA repair system includes base excision repair, nucleotide excision repair, mismatch repair, translesion replication, non-homologous end-joining, and recombinational repair. Homologous recombination performs the recombinational repair. The RAD51 gene is an ortholog of Esherichia coli recA, and the gene product Rad51 protein plays a central role in the homologous recombination. In mammals, 7 recA-like genes have been identified: RAD51, RAD51L1/B, RAD51L2/C, RAD51L3/D, XRCC2, XRCC3, and DMC1. These genes, with the exception of meiosis-specific DMC1, are essential for development in mammals. Disruption of the RAD51 gene leads to cell death, whereas RAD51L1/B, RAD51L2/C, RAD51L3/D, XRCC2, and XRCC3 genes (RAD51 paralogs) are not essential for viability of cells, but these gene-deficient cells exhibit a similar defective phenotype. Yeast two-hybrid analysis, co-immunoprecipitation, mutation analysis, and domain mapping of Rad51 and Rad51 paralogs have revealed protein-protein interactions among these gene products. Recent investigations have shown that Rad51 paralogs play a role not only in an early step, but also in a late step of homologous recombination. In addition, identification of alternative transcripts of some RAD51 paralogs may reflect the complexity of the homologous recombination system.
Association of Rad51 polymorphism with DNA repair in BRCA1 mutation carriers and sporadic breast cancer risk
Luisel J Ricks-Santi, Lara E Sucheston, Yang Yang, Jo L Freudenheim, Claudine J Isaacs, Marc D Schwartz, Ramona G Dumitrescu, Catalin Marian, Jing Nie, Dominica Vito, Stephen B Edge, Peter G Shields
BMC Cancer , 2011, DOI: 10.1186/1471-2407-11-278
Abstract: Peripheral blood lymphoblasts from women with known BRCA1 mutations underwent the MSA (n = 138 among 20 families). BRCA1 and Rad51 genotyping and sequencing were performed to identify SNPs and haplotypes associated with the MSA. Positive associations from the study in high-risk families were subsequently examined in a population-based case-control study of breast cancer (n = 1170 cases and 2115 controls).Breast cancer diagnosis was significantly associated with the MSA among women from BRCA1 families (OR = 3.2 95%CI: 1.5-6.7; p = 0.004). The Rad51 5'UTR 135 C>G genotype (OR = 3.64; 95% CI: 1.38, 9.54; p = 0.02), one BRCA1 haplotype (p = 0.03) and in a polygenic model, the E1038G and Q356R BRCA1 SNPs were significantly associated with MBPC (p = 0.009 and 0.002, respectively). The Rad51 5'UTR 135C genotype was not associated with breast cancer risk in the population-based study.Mutagen sensitivity might be a useful biomarker of penetrance among women with BRCA1 mutations because the MSA phenotype is partially explained by genetic variants in BRCA1 and Rad51.The genetic determinants of breast cancer are under intensive study. Some women with a strong family history of breast cancer inherit BRCA1 or BRCA2 mutations, which have a variable penetrance for breast cancer, between 40 to 66% [1], suggesting that additional factors contribute to cancer risk among BRCA1 and BRCA2 carriers. For sporadic cancers, however, many low-penetrant single-nucleotide polymorphisms (SNPs) have been investigated in pathways ranging from growth factor signaling to DNA repair. Yet, it has been difficult to find consistency across study results [2-4], due to differences in study populations, sample sizes and study designs [5]. However, studies of high risk populations generally help uncover the molecular mechanisms of a disease and provide guidance and direction for studies of sporadic disease. While BRCA1 and BRCA2 mutations are highly penetrant [1], resulting in higher risk for breast cancer,
Meiotic Recombination in Arabidopsis Is Catalysed by DMC1, with RAD51 Playing a Supporting Role  [PDF]
Olivier Da Ines,Fabienne Degroote,Chantal Goubely,Simon Amiard,Maria E. Gallego,Charles I. White
PLOS Genetics , 2013, DOI: 10.1371/journal.pgen.1003787
Abstract: Recombination establishes the chiasmata that physically link pairs of homologous chromosomes in meiosis, ensuring their balanced segregation at the first meiotic division and generating genetic variation. The visible manifestation of genetic crossing-overs, chiasmata are the result of an intricate and tightly regulated process involving induction of DNA double-strand breaks and their repair through invasion of a homologous template DNA duplex, catalysed by RAD51 and DMC1 in most eukaryotes. We describe here a RAD51-GFP fusion protein that retains the ability to assemble at DNA breaks but has lost its DNA break repair capacity. This protein fully complements the meiotic chromosomal fragmentation and sterility of Arabidopsis rad51, but not rad51 dmc1 mutants. Even though DMC1 is the only active meiotic strand transfer protein in the absence of RAD51 catalytic activity, no effect on genetic map distance was observed in complemented rad51 plants. The presence of inactive RAD51 nucleofilaments is thus able to fully support meiotic DSB repair and normal levels of crossing-over by DMC1. Our data demonstrate that RAD51 plays a supporting role for DMC1 in meiotic recombination in the flowering plant, Arabidopsis.
The Epistatic Relationship between BRCA2 and the Other RAD51 Mediators in Homologous Recombination  [PDF]
Yong Qing equal contributor,Mitsuyoshi Yamazoe equal contributor,Kouji Hirota,Donniphat Dejsuphong,Wataru Sakai,Kimiyo N. Yamamoto,Douglas K. Bishop,XiaoHua Wu,Shunichi Takeda
PLOS Genetics , 2011, DOI: 10.1371/journal.pgen.1002148
Abstract: RAD51 recombinase polymerizes at the site of double-strand breaks (DSBs) where it performs DSB repair. The loss of RAD51 causes extensive chromosomal breaks, leading to apoptosis. The polymerization of RAD51 is regulated by a number of RAD51 mediators, such as BRCA1, BRCA2, RAD52, SFR1, SWS1, and the five RAD51 paralogs, including XRCC3. We here show that brca2-null mutant cells were able to proliferate, indicating that RAD51 can perform DSB repair in the absence of BRCA2. We disrupted the BRCA1, RAD52, SFR1, SWS1, and XRCC3 genes in the brca2-null cells. All the resulting double-mutant cells displayed a phenotype that was very similar to that of the brca2-null cells. We suggest that BRCA2 might thus serve as a platform to recruit various RAD51 mediators at the appropriate position at the DNA–damage site.
XRCC3 and RAD51 Expression Are Associated with Clinical Factors in Breast Cancer  [PDF]
Jia Hu, Ning Wang, Ya-Jie Wang
PLOS ONE , 2013, DOI: 10.1371/journal.pone.0072104
Abstract: Aims XRCC3 and RAD51 are two important members in homologous recombination repair pathway. This study was performed to detect the expressions of these two molecules in breast cancer and explore their correlations with clinicopathological factors. Methods and Results Immunohistochemistry was used to detect protein expressions of XRCC3 and RAD51 in 248 cases of breast cancer tissue and 78 cases of adjacent non-cancerous tissue. Data showed that expressions for both XRCC3 and RAD51 were significantly increased in breast cancer. High XRCC3 expression was associated with large tumor size and positive PR and HER2 status, while high RAD51 expression was associated with axillary lymph node metastasis and positive PR and HER2 status. The result of multivariate analysis demonstrated that HER2, PR and RAD51 were significantly association with XRCC3. And besides XRCC3, axillary lymph node metastasis and PR were significantly correlated with RAD51. Conclusions XRCC3 and RAD51 were significantly associated with clinicopathological factors and they might play important roles in the development and progress of breast cancer.
Page 1 /100
Display every page Item

Copyright © 2008-2017 Open Access Library. All rights reserved.