Recombination-dependent deletion formation in mammalian cells deficient in the nucleotide excision repair gene 
            <i>ERCC1</i>

Sargent, R. Geoffrey; Rolig, Rhonda L.; Kilburn, April E.; Adair, Gerald M.; Wilson, John H.; Nairn, Rodney S.

doi:10.1073/pnas.94.24.13122

Cited by 72 publications

(88 citation statements)

References 61 publications

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“…The interaction of ERCC1-XPF with the single-stranded DNA binding replication protein A may be important in this regard (21). Finally, studies of deletion formation in ERCC1 knockout cells (22) suggest that the ERCC1 gene product is normally involved in a pathway leading to nonmutagenic processing of heteroduplex intermediates in recombination.…”

Section: Ercc1-xpf Cleaves Structures With a Psoralen Cross-link Locamentioning

confidence: 99%

Repair of an Interstrand DNA Cross-link Initiated by ERCC1-XPF Repair/Recombination Nuclease

Kuraoka

Kobertz²,

Ariza

et al. 2000

Journal of Biological Chemistry

266

228

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Interstrand DNA cross-link damage is a severe challenge to genomic integrity. Nucleotide excision repair plays some role in the repair of DNA cross-links caused by psoralens and other agents. However, in mammalian cells there is evidence that the ERCC1-XPF nuclease has a specialized additional function during interstrand DNA cross-link repair, beyond its role in nucleotide excision repair. We placed a psoralen monoadduct or interstrand cross-link in a duplex, 4 -6 bases from a junction with unpaired DNA. ERCC1-XPF endonucleolytically cleaved within the duplex on either side of the adduct, on the strand having an unpaired 3 tail. Crosslinks that were cleaved only on the 5 side were purified and reincubated with ERCC1-XPF. A second cleavage was then observed on the 3 side. Relevant partially unwound structures near a cross-link may be expected to arise frequently, for example at stalled DNA replication forks. The results show that the single enzyme ERCC1-XPF can release one arm of a cross-link and suggest a novel mechanism for interstrand cross-link repair.An important structure-specific DNA nuclease family in eukaryotes is represented by the ERCC1-XPF complex in mammalian cells and by the Rad1-Rad10 complex in Saccharomyces cerevisiae. These enzymes specifically cleave DNA near junctions between single-stranded and duplex DNA in cases where the single strand has a 5Ј33Ј polarity as it moves away from the junction (1-3). The ability of these enzymes to cut such bubble, flap, and Y structures is necessary for many DNA transactions. In mammalian cells, the heterodimeric ERCC1-XPF nuclease is formed by tight association of ERCC1 and XPF subunits (2, 4). Nucleotide excision repair (NER) 1 uses this nuclease to cleave a damaged DNA strand on the 5Ј side of an opened "bubble" intermediate formed around a lesion. Some strategies for repair of DNA double-stranded breaks in S. cerevisiae involve the use of Rad1-Rad10, sometimes in a complex with Msh2 and Msh3 (5). In these cases the nuclease aids in resolution of recombination intermediates by clipping off nonhomologous 3Ј single-stranded tails. In Drosophila, the XPF homolog mei9 is implicated in meiotic recombination (6). In the fission yeast Schizosaccharomyces pombe, the XPF homolog rad16 (swi9) and ERCC1 homolog swi10 are involved in the recombination events that lead to mating-type switching (7).NER-defective cells are sensitive to agents such as psoralen, which causes interstrand DNA cross-links (8). Beyond its participation in NER, however, ERCC1-XPF appears to have an additional role in the repair of interstrand DNA cross-links. It is known, for example, that ERCC1-defective and many XP group F cells are much more sensitive to DNA cross-linking agents than are other NER mutants (9, 10). Very little is known about the mechanism of repair of interstrand DNA cross-links. A number of pathways for cross-link repair can be envisaged. One possibility would mirror the model of Cole (11) for crosslink repair in Escherichia coli, which involves sequential NER and homologous...

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Section: Ercc1-xpf Cleaves Structures With a Psoralen Cross-link Locamentioning

confidence: 99%

Repair of an Interstrand DNA Cross-link Initiated by ERCC1-XPF Repair/Recombination Nuclease

Kuraoka

Kobertz²,

Ariza

et al. 2000

Journal of Biological Chemistry

266

228

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“…Although ERCC1 is not required for spontaneous recombination between repeated sequences (318), ercc1 Ϫ/Ϫ cell lines do exhibit defects in ends-in FIG. 15.…”

Section: Rad1/rad10mentioning

confidence: 99%

Role ofRAD52Epistasis Group Genes in Homologous Recombination and Double-Strand Break Repair

Symington

2002

Microbiol Mol Biol Rev

926

1,011

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The process of homologous recombination is a major DNA repair pathway that operates on DNA double-strand breaks, and possibly other kinds of DNA lesions, to promote error-free repair. Central to the process of homologous recombination are the RAD52 group genes (RAD50, RAD51, RAD52, RAD54, RDH54/TID1, RAD55, RAD57, RAD59, MRE11, and XRS2), most of which were identified by their requirement for the repair of ionizing-radiation-induced DNA damage in Saccharomyces cerevisiae. The Rad52 group proteins are highly conserved among eukaryotes, and Rad51, Mre11, and Rad50 are also conserved in prokaryotes and archaea. Recent studies showing defects in homologous recombination and double-strand break repair in several human cancer-prone syndromes have emphasized the importance of this repair pathway in maintaining genome integrity. Although sensitivity to ionizing radiation is a universal feature of rad52 group mutants, the mutants show considerable heterogeneity in different assays for recombinational repair of double-strand breaks and spontaneous mitotic recombination. Herein, I provide an overview of recent biochemical and structural analyses of the Rad52 group proteins and discuss how this information can be incorporated into genetic studies of recombination

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“…Site-specific recombination avoids the inherent instability of many random integrants (20,47,59), and targeting to the APRT locus allows us to make comparisons with previous results (63)(64)(65). These cell lines allowed us to test the effects of telomere sequence on gene expression, homologous recombination, gene rearrangements, and chromosome truncation.…”

mentioning

confidence: 99%

Insertion of a Telomere Repeat Sequence into a Mammalian Gene Causes Chromosome Instability

Kilburn

Shea

Sargent³

et al. 2001

Molecular and Cellular Biology

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Telomere repeat sequences cap the ends of eucaryotic chromosomes and help stabilize them. At interstitial sites, however, they may destabilize chromosomes, as suggested by cytogenetic studies in mammalian cells that correlate interstitial telomere sequence with sites of spontaneous and radiation-induced chromosome rearrangements. In no instance is the length, purity, or orientation of the telomere repeats at these potentially destabilizing interstitial sites known. To determine the effects of a defined interstitial telomere sequence on chromosome instability, as well as other aspects of DNA metabolism, we deposited 800 bp of the functional vertebrate telomere repeat, TTAGGG, in two orientations in the second intron of the adenosine phosphoribosyltransferase (APRT) gene in Chinese hamster ovary cells. In one orientation, the deposited telomere sequence did not interfere with expression of the APRT gene, whereas in the other it reduced mRNA levels slightly. The telomere sequence did not induce chromosome truncation and the seeding of a new telomere at a frequency above the limits of detection. Similarly, the telomere sequence did not alter the rate or distribution of homologous recombination events. The interstitial telomere repeat sequence in both orientations, however, dramatically increased gene rearrangements some 30-fold. Analysis of individual rearrangements confirmed the involvement of the telomere sequence. These studies define the telomere repeat sequence as a destabilizing element in the interior of chromosomes in mammalian cells.

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Recombination-dependent deletion formation in mammalian cells deficient in the nucleotide excision repair gene ERCC1

Cited by 72 publications

References 61 publications

Repair of an Interstrand DNA Cross-link Initiated by ERCC1-XPF Repair/Recombination Nuclease

Repair of an Interstrand DNA Cross-link Initiated by ERCC1-XPF Repair/Recombination Nuclease

Role ofRAD52Epistasis Group Genes in Homologous Recombination and Double-Strand Break Repair

Insertion of a Telomere Repeat Sequence into a Mammalian Gene Causes Chromosome Instability

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