XRCC2 and XRCC3, New Human Rad51-Family Members, Promote Chromosome Stability and Protect against DNA Cross-Links and Other Damages

Liu, Nan; Lamerdin, Jane E.; Tebbs, Robert S.; Schild, David; Tucker, James D.; Shen, Meng; Brookman, Kerry W.; Siciliano, Michael J.; Walter, Christi A.; Fan, Wufang; Narayana, Lakshmi S.; Zhou, Zi Qiang; Adamson, Aaron W.; Sorensen, Karen; Chen, David J.; Jones, Nigel J.; Thompson, Larry H.

doi:10.1016/s1097-2765(00)80078-7

Cited by 490 publications

(379 citation statements)

References 57 publications

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“…We first examined two hamster cell lines, Irs1 and Irs1SF, that are defective in the XRCC2 and XRCC3 genes, respectively [23]. These genes are homologues of RAD51 and are known to be involved in homologous recombination.…”

Section: Role Of Hr and Ner/translesion Bypass In Icl-mediated Stimulmentioning

confidence: 99%

Double-strand breaks induce homologous recombinational repair of interstrand cross-links via cooperation of MSH2, ERCC1-XPF, REV3, and the Fanconi anemia pathway

Zhang

Liu

et al. 2007

DNA Repair

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DNA interstrand cross-linking agents have been widely used in chemotherapeutic treatment of cancer. The majority of interstrand cross-links (ICLs) in mammalian cells are removed via a complex process that involves the formation of double strand breaks at replication forks, incision of the ICL, and subsequent error-free repair by homologous recombination. How double strand breaks effect the removal of ICLs and the downstream homologous recombination process is not clear. Here, we describe a plasmid-based recombination assay in which one copy of the CFP gene is inactivated by a site-specific psoralen ICL and can be repaired by gene conversion with a mutated homologous donor sequence. We found that the homology dependent recombination (HDR) is inhibited by the ICL. However, when we introduced a double strand break adjacent to the site of the ICL, the removal of the ICL was enhanced and the substrate was funneled into a HDR repair pathway. This process was not dependent on the nucleotide excision repair pathway, but did require the ERCC1-XPF endonuclease and REV3. In addition, both the Fanconi anemia pathway and the mismatch repair protein MSH2 were required for the recombinational repair processing of the ICL. These results suggest that the juxtaposition of an ICL and a DSB stimulates repair of ICLs through a process requiring components of mismatch repair, ERCC1-XPF, REV3, Fanconi anemia proteins, and homologous recombination repair factors.

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Section: Role Of Hr and Ner/translesion Bypass In Icl-mediated Stimulmentioning

confidence: 99%

Double-strand breaks induce homologous recombinational repair of interstrand cross-links via cooperation of MSH2, ERCC1-XPF, REV3, and the Fanconi anemia pathway

Zhang

Liu

et al. 2007

DNA Repair

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“…In this respect, it is interesting to note that the mammalian RAD51 gene family contains at least seven different genes whose specific functions are under investigation. 20,[42][43][44][45][46] It is possible that different homologous recombination processes make use of variable sets of gene products, or that accessory proteins are present at variable levels. hRAD51 overexpression might only enhance gene targeting threefold before another component of the recombination machinery becomes limiting, and this could be different for intrachromosomal recombination.…”

Section: Figure 4 Survival Of Hrad51 Overexpressing Cells To Ionisingmentioning

confidence: 99%

Gene targeting is enhanced in human cells overexpressing hRAD51

Yáñez

Porter

1999

Gene Ther

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The ideal therapy for single gene disorders would be repair approach, we have overexpressed the gene encoding of the mutated disease genes. Homologous recombination hRAD51, a protein with homologous DNA pairing and is one of several cellular mechanisms for the repair of DNA strand exchange activities, in human cells and measured damage. Recombination between exogenous DNA and its effect on gene targeting. We report a two-to three-fold homologous chromosomal loci (gene targeting) can be increase in gene targeting, and enhanced resistance to used to repair an endogenous gene, but the low efficiency ionising radiation in hRAD51-overexpressing cells with no of this process is a serious barrier to its therapeutic potenobvious detrimental effects. These observations provide tial. Recent progress in the isolation and characterisation valuable genetic evidence for the involvement of hRAD51 of mammalian genes and proteins involved in DNA recomin both gene targeting and DNA repair in human cells. Our bination has raised the possibility that the cellular biochemdata also establish overexpression of recombination genes istry of recombination can be manipulated to improve the as a viable approach to improving gene targeting efficiency of gene targeting. As an initial test of this efficiencies.

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“…The second and alternative strategy is non-homologous end joining (NHEJ), which ligates the DNA ends without requiring sequence homologies between the two interacting molecules. Defects in HR or in NHEJ can lead to genome instability and tumorigenesis (Liu et al, 1998;Sonoda et al, 1998;Difilippantonio et al, 2000;Ferguson et al, 2000a;Bertrand et al, 2003). However, both functional HR and NHEJ can be responsible for genome rearrangements: (i) functional HR between repeated sequences dispersed through the genome can also lead to genome rearrangements (Purandare and Patel, 1997;Richardson and Jasin, 2000b;Bertrand et al, 2004), and (ii) functional Ku autoantigen protein (KU)-dependent as well as KU-independent NHEJ can generate genetic rearrangements (Guirouilh-Barbat et al, 2004).…”

Section: Introductionmentioning

confidence: 99%

XRCC4 in G1 suppresses homologous recombination in S/G2, in G1 checkpoint-defective cells

et al. 2006

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Non-homologous end joining (NHEJ) and homologous recombination (HR) are two pathways that can compete or cooperate for DNA double-strand break (DSB) repair. NHEJ was previously shown to act throughout the cell cycle whereas HR is restricted to late S/G2. Paradoxically, we show here that defect in XRCC4 (NHEJ) leads to over-stimulation of HR when cells were irradiated in G1, not in G2. However, XRCC4 defect did not modify the strict cell cycle regulation for HR (i.e. in S/G2) as attested by (i) the formation of Rad51 foci in late S/G2 whatever the XRCC4 status, and (ii) the fact that neither Rad51 foci nor HR (gene conversion plus single-strand annealing) events induced by ionizing radiation were detected when cells were maintained blocked in G1. Finally, both c-H2AX analysis and pulse field gel electrophoresis showed that following irradiation in G1, some DSBs reached S/G2 in NHEJ-defective cells. Taken together, our results show that when cells are defective in G1/S arrest, DSB produced in G1 and left unrepaired by XRCC4 can be processed by HR but in late S/G2.

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XRCC2 and XRCC3, New Human Rad51-Family Members, Promote Chromosome Stability and Protect against DNA Cross-Links and Other Damages

Cited by 490 publications

References 57 publications

Double-strand breaks induce homologous recombinational repair of interstrand cross-links via cooperation of MSH2, ERCC1-XPF, REV3, and the Fanconi anemia pathway

Double-strand breaks induce homologous recombinational repair of interstrand cross-links via cooperation of MSH2, ERCC1-XPF, REV3, and the Fanconi anemia pathway

Gene targeting is enhanced in human cells overexpressing hRAD51

XRCC4 in G1 suppresses homologous recombination in S/G2, in G1 checkpoint-defective cells

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