XRCC1 Polypeptide Interacts with DNA Polymerase   and Possibly Poly (ADP-Ribose) Polymerase, and DNA Ligase III Is a Novel Molecular 'Nick-Sensor' In Vitro

Caldecott, Keith W.; Aoufouchi, Saïd; Johnson, Penny A.; Shall, Sydney

doi:10.1093/nar/24.22.4387

Cited by 566 publications

(438 citation statements)

References 24 publications

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“…It is conceivable that the steps subsequent to topoisomerase I removal by this repair enzyme could involve some mechanism common to the BER pathway. Recently it has been proposed that BER is accomplished by a multiprotein complex consisting of PARP, XRCC1, DNA polymerase β and DNA ligase II (Caldecott et al, 1996;Mason et al, 1998). Interestingly, EM9 cells with defective XRCC1 are hypersensitive to camptothecin (Caldecott and Jeggo, 1991) but not etoposide (Jeggo et al, 1989).…”

Section: Discussionmentioning

confidence: 99%

Differential effects of the poly (ADP-ribose) polymerase (PARP) inhibitor NU1025 on topoisomerase I and II inhibitor cytotoxicity in L1210 cells in vitro

et al. 2001

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The potent novel poly(ADP-ribose) polymerase (PARP) inhibitor, NU1025, enhances the cytotoxicity of DNA-methylating agents and ionizing radiation by inhibiting DNA repair. We report here an investigation of the role of PARP in the cellular responses to inhibitors of topoisomerase I and II using NU1025. The cytotoxicity of the topoisomerase I inhibitor, camptothecin, was increased 2.6-fold in L1210 cells by co-incubation with NU1025. Camptothecin-induced DNA strand breaks were also increased 2.5-fold by NU1025 and exposure to camptothecin-activated PARP. In contrast, NU1025 did not increase the DNA strand breakage or cytotoxicity caused by the topoisomerase II inhibitor etoposide. Exposure to etoposide did not activate PARP even at concentrations that caused significant levels of apoptosis. Taken together, these data suggest that potentiation of camptothecin cytotoxicity by NU1025 is a direct result of increased DNA strand breakage, and that activation of PARP by camptothecin-induced DNA damage contributes to its repair and consequently cell survival. However, in L1210 cells at least, it would appear that PARP is not involved in the cellular response to etoposide-mediated DNA damage. On the basis of these data, PARP inhibitors may be potentially useful in combination with topoisomerase I inhibitor anticancer chemotherapy. © 2001 Cancer Research Campaign http://www.bjcancer.com

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Section: Discussionmentioning

confidence: 99%

Differential effects of the poly (ADP-ribose) polymerase (PARP) inhibitor NU1025 on topoisomerase I and II inhibitor cytotoxicity in L1210 cells in vitro

et al. 2001

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“…Likewise, XRCC1 impacts repair of single-strand breaks via the ternary complex of XRCC1, LigIIIα and PARP1 [15,18]. PARP1 is believed to be involved in the sensing of DNA nicks (BER intermediates) [70], acting in conjunction with XRCC1 as a scaffold for the recruitment of gap-tailoring enzymes.…”

Section: Scaffold Proteinsmentioning

confidence: 99%

“…SSBR, on the other hand, is defined specifically for the repair of single-strand breaks in DNA arising from irradiation, incomplete topoisomerase action or ROS byproducts of metabolism [14]. PARP1 recognizes the single-strand break, signaling recruitment of repair proteins to the damaged site [15]. One of the first proteins recruited is XRCC1, a protein closely associated with BER pathway coordination.…”

Section: Introduction Of a Unifying Ber Modelmentioning

confidence: 99%

A unified view of base excision repair: Lesion-dependent protein complexes regulated by post-translational modification

Almeida¹,

Sobol²

2007

DNA Repair

386

374

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Base excision repair (BER) proteins act upon a significantly broad spectrum of DNA lesions that result from endogenous and exogenous sources. Multiple sub-pathways of BER (short-path or longpatch) and newly designated DNA repair pathways (e.g., SSBR and NIR) that utilize BER proteins complicate any comprehensive understanding of BER and its role in genome maintenance, chemotherapeutic response, neurodegeneration, cancer or aging. Herein, we propose a unified model of BER, comprised of three functional processes: Lesion Recognition/Strand Scission, Gap Tailoring and DNA Synthesis/Ligation, each represented by one or more multiprotein complexes and coordinated via the XRCC1/DNA Ligase III and PARP1 scaffold proteins. BER therefore may be represented by a series of repair complexes that assemble at the site of the DNA lesion and mediates repair in a coordinated fashion involving protein-protein interactions that dictate subsequent steps or sub-pathway choice. Complex formation is influenced by post-translational protein modifications that arise from the cellular state or the DNA damage response, providing an increase in specificity and efficiency to the BER pathway. In this review, we have summarized the reported BER proteinprotein interactions and protein post-translational modifications and discuss the impact on DNA repair capacity and complex formation.

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“…XRCC1 plays an important role in the base excision repair pathway, and interacts with DNA polymerase b, PARP and DNA ligase III. It also has a BRCT domain, which is characteristic of proteins involved in cycle checkpoint functions and this domain may be responsive to DNA damage (Caldecott et al, 1996;Masson et al, 1998). Abdel-Rahman and El-Zein (2000) found that the 399Gln polymorphism of XRCC1 appeared to be associated with reduced repair of NNK-induced genetic damage in cultured human lymphocytes.…”

mentioning

confidence: 99%

p53 polymorphisms associated with mutations in and loss of heterozygosity of the p53 gene in male oral squamous cell carcinomas in Taiwan

Huang

et al. 2004

Br J Cancer

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The present study was designed to examine whether different p53 haplotypes of exon 4 -intron 3 -intron 6 affect the frequency of mutations and loss of heterozygosity (LOH) of the p53 gene in male oral squamous cell carcinomas (OSCCs) in Taiwan. We found that individuals without two Pro-W-G alleles had significantly higher frequency of p53 mutations than those with two Pro-W-G alleles (odds ratio (OR) ¼ 1.98; 95% confidence interval (CI), 1.10 -3.56). Out of the 172 p53 gene exon 4 informative male OSCCs, 72 (41.9%) showed LOH. Among these 72 OSCCs with LOH, the frequency of Pro allele loss was 73.6% (53/72). It is notable that alcohol drinking increased the frequency of Arg allele loss (OR ¼ 10.56; 95% CI, 1.23 -234.94) in OSCCs from patients who both smoked cigarettes and chewed areca quid (AQ). The frequency of LOH of p53 was not different between p53-mutated OSCCs and p53-normal OSCCs. Thus, the present study revealed that (a) the Arg allele is associated with p53 mutations, (b) the Pro allele is preferentially lost in OSCCs associated with cigarette smoking and AQ chewing, while the frequency of Arg allele loss is increased with alcohol drinking, and (c) haploinsufficiency of p53 is in itself likely to contribute to tumour progression in Taiwanese OSCCs.

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XRCC1 Polypeptide Interacts with DNA Polymerase and Possibly Poly (ADP-Ribose) Polymerase, and DNA Ligase III Is a Novel Molecular 'Nick-Sensor' In Vitro

Cited by 566 publications

References 24 publications

Differential effects of the poly (ADP-ribose) polymerase (PARP) inhibitor NU1025 on topoisomerase I and II inhibitor cytotoxicity in L1210 cells in vitro

Differential effects of the poly (ADP-ribose) polymerase (PARP) inhibitor NU1025 on topoisomerase I and II inhibitor cytotoxicity in L1210 cells in vitro

A unified view of base excision repair: Lesion-dependent protein complexes regulated by post-translational modification

p53 polymorphisms associated with mutations in and loss of heterozygosity of the p53 gene in male oral squamous cell carcinomas in Taiwan

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