Role of RAD51C and XRCC3 in Genetic Recombination and DNA Repair

Liu, Yilun; Tarsounas, Madalena; O'Regan, Paul; West, Stephen C.

doi:10.1074/jbc.m609066200

Cited by 106 publications

(86 citation statements)

References 44 publications

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“…Indeed, XRCC3 depletion also was found to affect CHK2 phosphorylation (20). The CX3 complex also has been implicated in late stages of HR (54). However, mechanistically how the CX3 complex controls these independent functions requires further investigation.…”

Section: Discussionmentioning

confidence: 99%

Distinct Roles of FANCO/RAD51C Protein in DNA Damage Signaling and Repair

Somyajit

Subramanya

Nagaraju

2012

Journal of Biological Chemistry

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Background: RAD51C plays a key role in recombinational repair and genome stability. Results: RAD51C deficiency leads to repair as well as a signaling defect in response to interstrand cross-links and double strand breaks. Conclusion: RAD51C is critical for Fanconi anemia pathway of ICL repair and intra-S-phase checkpoint. Significance: This study identifies distinct roles of RAD51C in repair and signaling and as a tumor suppressor.

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Section: Discussionmentioning

confidence: 99%

Distinct Roles of FANCO/RAD51C Protein in DNA Damage Signaling and Repair

Somyajit

Subramanya

Nagaraju

2012

Journal of Biological Chemistry

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“…XRCC3 is thought to participate in the resolvase step and RAD51C in both the resolvase step and in presynapsis of HR repair [24][25]. Thus, our data strongly suggest that DNA double strand breaks, associated with DNA replication, underlie Cr(VI)-induced chromatid aberrations, particularly chromatid exchanges.…”

Section: Discussionmentioning

confidence: 53%

“…XRCC3 is thought to participate in the resolvase step of HR repair and RAD51C is thought to participate in both the resolvase step and in presynapsis [24][25]. It is unknown if either of these genes are is involved in preventing Cr(VI)-induced CIN.…”

Section: Introductionmentioning

confidence: 99%

Homologous recombination repair protects against particulate chromate-induced chromosome instability in Chinese hamster cells

Stackpole

Wise

Goodale

et al. 2007

Mutation Research/Fundamental and Molecular Mechanisms of Mutag

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Particulate hexavalent chromium [Cr(VI)] compounds are well-established human carcinogens. Cr (VI)-induced tumors are characterized by chromosomal instability (CIN); however, the mechanisms of this effect are unknown. We investigated the hypothesis that homologous recombination (HR) repair of DNA double strand breaks protect cells from Cr(VI)-induced CIN by focusing on the XRCC3 and RAD51C genes, which play an important role in cellular resistance to DNA double strand breaks. We used Chinese hamster cells defective in each HR gene (irs3 for RAD51C and irs1SF for XRCC3) and compared with their wildtype parental and cDNA-complemented controls. We found that the intracellular Cr ion levels varied among the cell lines after particulate chromate treatment. Importantly, accounting for differences in Cr ion levels, we discovered that XRCC3 and RAD51C cells treated with lead chromate had increased cytotoxicity and chromosomal aberrations, relative to wild-type and cDNA-complimented cells. We also observed the emergence of high levels of chromatid exchanges in the two mutant cell lines. For example, 1 ug/cm 2 lead chromate induced 20 and 32 exchanges in XRCC3-and RAD51C-deficient cells, respectively, whereas no exchanges were detected in the wildtype and cDNA-complemented cells. These observations suggest that HR protects cells from Cr(VI)-induced CIN, consistent with the ability of particulate Cr(VI) to induce double strand breaks.

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“…Some previous reports that have described the interaction between RAD51C and XRCC3, and the role of RAD51C in the resolution of homologous recombination intermediates have also been evaluated (15,31). In addition, some studies have suggested that RAD51C expression can affect XRCC3 expression.…”

Section: Discussionmentioning

confidence: 99%

RAD51C-Deficient Cancer Cells Are Highly Sensitive to the PARP Inhibitor Olaparib

Min

Yoon

et al. 2013

Molecular Cancer Therapeutics

122

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A PARP inhibitor is a rationally designed targeted therapy for cancers with impaired DNA repair abilities. RAD51C is a paralog of RAD51 that has an important role in the DNA damage response. We found that cell lines sensitive to a novel oral PARP inhibitor, olaparib, had low levels of RAD51C expression using microarray analysis, and we therefore hypothesized that low expression of RAD51C may hamper the DNA repair process, resulting in increased sensitivity to olaparib. Compared with the cells with normal RAD51C expression levels, RAD51C-deficient cancer cells were more sensitive to olaparib, and a higher proportion underwent cell death by inducing G 2 -M cell-cycle arrest and apoptosis. The restoration of RAD51C in a sensitive cell line caused attenuation of olaparib sensitivity. In contrast, silencing of RAD51C in a resistant cell line enhanced the sensitivity to olaparib, and the number of RAD51 foci decreased with ablated RAD51C expression. We also found the expression of RAD51C was downregulated in cancer cells due to epigenetic changes and RAD51C expression was low in some gastric cancer tissues. Furthermore, olaparib significantly suppressed RAD51C-deficient tumor growth in a xenograft model. In summary, RAD51C-deficient cancer cells are highly sensitive to olaparib and offer preclinical proof-of-principle that RAD51C deficiency may be considered a biomarker for predicting the antitumor effects of olaparib. Mol Cancer Ther; 12(6); 865-77. Ó2013 AACR.

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Role of RAD51C and XRCC3 in Genetic Recombination and DNA Repair

Cited by 106 publications

References 44 publications

Distinct Roles of FANCO/RAD51C Protein in DNA Damage Signaling and Repair

Distinct Roles of FANCO/RAD51C Protein in DNA Damage Signaling and Repair

Homologous recombination repair protects against particulate chromate-induced chromosome instability in Chinese hamster cells

RAD51C-Deficient Cancer Cells Are Highly Sensitive to the PARP Inhibitor Olaparib

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