XRCC3 promotes homology-directed repair of DNA damage in mammalian cells

Pierce, Andrew J.; Johnson, Roger D.; Thompson, Larry H.; Jasin, Maria

doi:10.1101/gad.13.20.2633

Cited by 1,242 publications

(1,525 citation statements)

References 39 publications

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“…To study the effects of Hus1 on HRR efficiency following DNA DSBs, we combined the pDR-GFP-ISceI system (Pierce et al, 1999) and siRNA approaches. The I-SceI system can be used to examine the types of recombination events induced by DSBs at a defined chromosomal locus in mammalian cells by the nuclease Figure 1 Hus1 deficient cells are much more sensitive to IRinduced killing than their Hus1-positive counterparts.…”

Section: Hus1 Sirnas Inhibits Hrr Efficiencymentioning

confidence: 99%

“…I-SceI, which is known to stimulate recombination in mammalian cells. The advantage of pDR-GFP-I-SceI system is using a modified gene for green fluorescent protein (GFP) as a recombination reporter (Pierce et al, 1999). The 18-bp I-SceI site is inserted within GFP gene and inactivates it.…”

Section: Hus1 Sirnas Inhibits Hrr Efficiencymentioning

confidence: 99%

“…When the DSBs are induced by I-SceI endonuclease, a homologous repair event with a linked donor GFP gene fragment restores functional GFP expression. These gene conversion events can be readily detected by flow cytometry in 2-4 days (Pierce et al, 1999).…”

Section: Hus1 Sirnas Inhibits Hrr Efficiencymentioning

confidence: 99%

“…To evaluate HRR of DNA DSBs, we first established the stable cell lines (F-DRGFP cells) that have incorporated the substrate of I-SceI endonuclease by transfecting the pDR-GFP plasmid (provided by Dr Jasin) (Pierce et al, 1999) to transformed mouse kidney fibroblast cells (Hu et al, 2005). Then we transfected F-DRGFP cells with the plasmid that encoded I-SceI endonuclease to observe the intensity of GFP signals measured by flow cytometry.…”

Section: Hus1 Sirnas Inhibits Hrr Efficiencymentioning

confidence: 99%

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The effect of Hus1 on ionizing radiation sensitivity is associated with homologous recombination repair but is independent of nonhomologous end-joining

Wang

Weiss

et al. 2006

Oncogene

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Mammalian Hus1 plays an important role in maintaining genomic integrity. Cells lacking mouse Hus1 are hypersensitive to DNA damage inducers including UV and camptothecin (CPT). By using clonogenic assay, we show here that Hus1 deficient mouse cells are hypersensitive to ionizing radiation (IR) compared with their Hus1-positive counterparts. However, these cells show similar induction levels and similar rejoining rates of DNA double strand breaks (DSBs) following IR, indicating that the effect of Hus1 on cell radiosensitivity is independent of nonhomologous end-joining (NHEJ). By combining an I-SceIinduced-DNA DSBs system and a siRNA approach, we also show that knocking down Hus1 decreases the efficiency of homologous recombination repair (HRR), which is associated with the cellular sensitivity to IRinduced killing. Together, these results indicate that the role of Hus1 affecting the sensitivity of cells to IR-induced killing is independent of NHEJ but might be linked to HRR.

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Section: Hus1 Sirnas Inhibits Hrr Efficiencymentioning

confidence: 99%

Section: Hus1 Sirnas Inhibits Hrr Efficiencymentioning

confidence: 99%

Section: Hus1 Sirnas Inhibits Hrr Efficiencymentioning

confidence: 99%

Section: Hus1 Sirnas Inhibits Hrr Efficiencymentioning

confidence: 99%

See 2 more Smart Citations

The effect of Hus1 on ionizing radiation sensitivity is associated with homologous recombination repair but is independent of nonhomologous end-joining

Wang

Weiss

et al. 2006

Oncogene

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“…LIG4 and XRCC4 proteins are then recruited to ligate and fill the gap in the broken DNA strands (12). Deficiencies in these DSB repair genes have been extensively reported to be associated with high incidence of chromosome aberrations, elevated radiation sensitivity, and tumorigenesis (13)(14)(15)(16). DNA polymorphisms of DSB pathway genes have also been found to be significantly associated with the etiology of many malignancies, including breast, lung, skin, and epithelial ovarian cancers (17)(18)(19)(20)(21)(22).…”

Section: Introductionmentioning

confidence: 99%

Genetic polymorphisms in double-strand break DNA repair genes associated with risk of oral premalignant lesions

Yang

Lippman

Huang

et al. 2008

European Journal of Cancer

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Oral premalignant lesions (OPLs) are early genetic events en route to oral cancer. To identify individuals susceptible to OPL is critical to the prevention of oral cancer. In a case-control study consisting of 147 patients with histologically confirmed OPL and 147 matched controls, we evaluated the associations of 10 genetic variants in nine genes of the double-strand break (DSB) DNA repair pathway with OPL risk. The most notable finding was an intronic polymorphism (A17893G) of the XRCC3 gene. Compared with the homozygous wild-type AA genotype, the odds ratios [OR] (95% confidence interval [CI]) for the heterozygous AG and homozygous variant GG genotype were 0.85 (0.49-1.48) and 0.18 (0.07-0.47), respectively (P for trend=0.002). In addition, compared with the most common A-C haplotype of XRCC3 (in the order of A17893G-T241M), the G-C haplotype was associated with a significantly decreased risk of OPL (OR=0.40, 95% CI 0.23-0.68). Moreover, compared with individuals without the G-C haplotype, the ORs were 1.04 (0.56-1.95) and 0.20 (0.08-0.51) for subjects with one copy and two copies of the G-C haplotype, respectively (P for trend=0.005). Classification and regression tree (CART) analysis further revealed potential highorder gene-gene and gene-environmental interactions and categorized subjects into different risk groups according to their specific polymorphic signatures. Overall, our study provides the first epidemiological evidence supporting a connection between DSB gene variants and OPL development. Our data also suggest that the effects of high-order interactions should be taken into consideration when evaluating OPL predisposition.

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Midgestation lethality in mice deficient for the RecA-related gene,Rad51d/Rad51l3

Pittman

Schimenti

2000

genesis

140

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Summary: Homologous recombination (HR) occurs in all organisms, and is important for repair of DNA damage, chromosome segregation during meiosis, and genetic diversification. Genes critical for recombinational DNA repair and meiotic recombination include members of the RecA/RAD51 family, of which seven have been identified in mammals. Here, we describe the disruption of Rad51d (recently designated Rad51l3) in mice and its phenotypic consequences. Rad51d‐deficient mice die between 8.5 and 11.5 dpc. The affected embryos are smaller than littermates, posteriorly truncated, and developmentally delayed. Embryonic fibroblasts from mutant embryos could not be propagated more than one generation in culture. Rad51d‐deficient blastocysts were not sensitive to gamma radiation or methylmethanesulfonate (MMS) in blastocyst outgrowth experiments. The variable and generalized developmental progression defects in Rad51d‐deficient embryos suggests that mutant cells may undergo delayed or suboptimal repair of DNA damage, resulting in accumulated degrees of mutation and/or cell cycle perturbation that are incompatible with normal embryonic development. genesis 26:167–173, 2000. © 2000 Wiley‐Liss, Inc.

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XRCC3 promotes homology-directed repair of DNA damage in mammalian cells

Cited by 1,242 publications

References 39 publications

The effect of Hus1 on ionizing radiation sensitivity is associated with homologous recombination repair but is independent of nonhomologous end-joining

The effect of Hus1 on ionizing radiation sensitivity is associated with homologous recombination repair but is independent of nonhomologous end-joining

Genetic polymorphisms in double-strand break DNA repair genes associated with risk of oral premalignant lesions

Midgestation lethality in mice deficient for the RecA-related gene,Rad51d/Rad51l3

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