Differential and collaborative actions of Rad51 paralog proteins in cellular response to DNA damage

Yonetani, Yasukazu; Hochegger, Helfrid; Sonoda, Eiichiro; Shinya, Sayoko; Yoshikawa, Hideki; Takeda, Shunichi; Yamazoe, Mistuyoshi

doi:10.1093/nar/gki766

Cited by 77 publications

(83 citation statements)

References 48 publications

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“…Consistent with this notion, an xrcc3/rad51d double deletion in DT40, involving proteins from both the BCDX2 and RAD51C-XRCC3 complexes, exhibits a greater DNA repair defect than either of the two single deletions (22). In the work reported here, we further define the roles played by the RAD51C-XRCC3 complex.…”

supporting

confidence: 78%

Role of RAD51C and XRCC3 in Genetic Recombination and DNA Repair

Liu¹,

Tarsounas²,

O'Regan³

et al. 2007

Journal of Biological Chemistry

106

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In germ line cells, recombination is required for gene reassortment and proper chromosome segregation at meiosis, whereas in somatic cells it provides an important mechanism for the repair of DNA double-strand breaks. Five proteins (RAD51B, RAD51C, RAD51D, XRCC2, and XRCC3) that share homology with RAD51 recombinase and are known as the RAD51 paralogs are important for recombinational repair, as paralog-defective cell lines exhibit spontaneous chromosomal aberrations, defective DNA repair, and reduced gene targeting. The paralogs form two distinct protein complexes, RAD51B-RAD51C-RAD51D-XRCC2 and RAD51C-XRCC3, but their precise cellular roles remain unknown. Here, we show that, like MLH1, RAD51C localized to mouse meiotic chromosomes at pachytene/diplotene. Using immunoprecipitation and gel filtration analyses, we found that Holliday junction resolvase activity associated tightly and co-eluted with the 80-kDa RAD51C-XRCC3 complex. Taken together, these data indicate that the RAD51C-XRCC3-associated Holliday junction resolvase complex associates with crossovers and may play an essential role in the resolution of recombination intermediates prior to chromosome segregation.

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supporting

confidence: 78%

Role of RAD51C and XRCC3 in Genetic Recombination and DNA Repair

Liu¹,

Tarsounas²,

O'Regan³

et al. 2007

Journal of Biological Chemistry

106

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“…Mutant cell lines deficient in the Rad51 paralogs and Brca2 have also been generated in chicken B-lymphocyte DT40 cells, all of which exhibited reduced levels of spontaneous and mitomycin C (MMC)-induced SCEs [19][20][21][22]. In all the hamster and chicken Rad51 paralog mutants, the formation of Rad51 nuclear foci is severely impaired following treatment with DNA damaging agents (typically IR and MMC).…”

Section: Introductionmentioning

confidence: 99%

Low doses of alpha particles do not induce sister chromatid exchanges in bystander Chinese hamster cells defective in homologous recombination

et al. 2008

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We reported previously that the homologous recombinational repair (HRR)-deficient Chinese hamster mutant cell line irs3 (deficient in the Rad51 paralog Rad51C) showed only a 50% spontaneous frequency of sister chromatid exchange (SCE) as compared to parental wildtype V79 cells. Furthermore, when irradiated with very low doses of alpha particles, SCEs were not induced in irs3 cells, as compared to a prominent bystander effect observed in V79 cells (Nagasawa et al., Radiat. Res. 164, 141-147, 2005). In the present study, we examined additional Chinese hamster cell lines deficient in the Rad51 paralogs Rad51C, Rad51D, Xrcc2, and Xrcc3 as well as another essential HRR protein, Brca2. Spontaneous SCE frequencies in non-irradiated wild-type cell lines CHO, AA8 and V79 were 0.33 SCE/chromosome, whereas two Rad51C-deficient cell lines showed only 0.16 SCE/chromosome. Spontaneous SCE frequencies in cell lines defective in Rad51D, Xrcc2, Xrcc3, and Brca2 ranged from 0.23-0.33 SCE/chromosome, 0-30% lower than wild-type cells. SCEs were induced significantly 20-50% above spontaneous levels in wild-type cells exposed to a mean dose of 1.3 mGy of alpha particles (<1% of nuclei traversed by an alpha particle). However, induction of SCEs above spontaneous levels was minimal or absent after α-particle irradiation in all of the HRR-deficient cell lines. These data suggest that Brca2 and the Rad51 paralogs contribute to DNA damage repair processes induced in bystander cells (presumably oxidative damage repair in S-phase cells) following irradiation with very low doses of alpha particles.3

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“…Smirado et al (2005) have shown that p53-and rad51d-double defective mouse embryonic fibroblasts are cisplatinsensitive. Yonetani et al (2005) also recently reported that rad51d-deficient chicken DT40 cells are extremely sensitive to cisplatin and that both wild type and rad51d-deficient cells are similarly radioresistant. Their study used p53-defective DT40 cells.…”

Section: Discussionmentioning

confidence: 87%

“…RAD51D is important for both DNA repair and telomere maintenance, and is therefore essential for cell viability. In addition, deletion mutants of rad51 paralogs including rad51d in chicken DT40 cells that harbor a p53 defect are highly sensitive to cisplatin compared with wild type cells (Yonetani et al, 2005). Similarly, Smiraldo et al (2005) reported that double mutants of rad51d and p53 are more sensitive to DNA-damaging agent than p53 single mutants.…”

Section: Introductionmentioning

confidence: 98%

X-ray Irradiation Altered Chemosensitivity of a p53-null Non-small Cell Lung Cancer Cell Line

Tsutsumi

Yasuda

Nishioka

2006

Cell Struct. Funct.

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ABSTRACT. Radiotherapy is an effective approach to treating many types of cancer. Recent progress in radiotherapy technology, such as intensity-modulated radiation therapy (IMRT) and three-dimensional (3D) radiotherapy, allow precise energy transfer to the tumor, which has improved local control rates. However, the emergence of tolerant cells during or after radiotherapy remains problematic. In the present study, we first established a cell population from H1299, the p53-null non-small cell lung cancer cell line, by 10 Gy irradiation using 6 MV X-rays. The radio-and chemosensitivity of this cell population (referred to as H1299-IR) was determined using colony formation analyses and MTS assays. Compared with the parental cell line, the radiosensitivity of H1299-IR was apparently the same. H1299 and H1299-IR were both more radio tolerant than the A549 cell line. However, H1299-IR became significantly more sensitive to cisplatin, an antitumor agent. After exposure to 25 µg/ ml cisplatin for 2 h, parental cells steadily grew during the MTS assay, whereas the sensitivity of H1299-IR cells doubled both at 24 and 48 h. Microarray analysis of over 30,000 H1299-IR genes (Agilent Technology) revealed that 12 and 15 genes were up-(>2.0) and down-(<2.0) regulated, respectively. Rad51d (homologous recombination repair protein) gene was down-regulated 2.8-fold, whereas matrix metalloproteinase 1 (collagenase-1) gene was up-regulated 4.4-fold. These results indicated that some p53-null non-small cell lung cancers could be successfully treated when X-ray radiotherapy was administered with subsequent or concurrent cisplatin chemotherapy.

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Differential and collaborative actions of Rad51 paralog proteins in cellular response to DNA damage

Cited by 77 publications

References 48 publications

Role of RAD51C and XRCC3 in Genetic Recombination and DNA Repair

Role of RAD51C and XRCC3 in Genetic Recombination and DNA Repair

Low doses of alpha particles do not induce sister chromatid exchanges in bystander Chinese hamster cells defective in homologous recombination

X-ray Irradiation Altered Chemosensitivity of a p53-null Non-small Cell Lung Cancer Cell Line

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