Flowchart: Preparation: Xrcc11

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Text Box: Ape1                     

                                                     

                                   

Cancer:

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lung

Text Box: Xrcc1
 


                                    

                                     

                                                         

                                                       

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Carcinogenesis. 2006 Apr 18; [Epub ahead of print]

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Genetic variants of the ADPRT, XRCC1, and APE1 genes and risk of cutaneous melanoma.

Li C, Liu Z, Wang LE, Strom SS, Lee JE, Gershenwald JE, Ross MI, Mansfield PF, Cormier JN, Prieto VG, Duvic M, Grimm EA, Wei Q.

Department of Epidemiology, The University of Texas M. D. Anderson Cancer Center, Houston, Texas, USA.

Sunlight causes various kinds of DNA damage, including oxidative lesions that are removed effectively by the base excision repair (BER) pathway, in which ADPRT, XRCC1, and APE1 play a key role. However, genetic variation in these genes may alter their functions. We hypothesized that ADPRT, XRCC1, and APE1 polymorphisms are associated with risk of cutaneous melanoma (CM). In a hospital-based case-control study of 602 CM patients and 603 cancer-free control subjects frequency matched on age, sex, and ethnicity, we genotyped for three non-synonymous single-nucleotide polymorphisms (SNPs) (i.e., the ADPRT Val762Ala, XRCC1 Arg399Gln, and APE1Asp148Glu) and assessed their associations with risk of CM. We found no significant difference in the allele frequencies between cases and controls for any of these three SNPs. However, we found that, compared with the APE1 Asp/Asp genotype, a significantly decreased risk of CM was associated with the APE1 Asp/Glu (adjusted odds ratio [OR] = 0.60, 95% confidence interval [CI] = 0.41-0.86), Glu/Glu (OR = 0.58, 95% CI = 0.38-0.88) and combined APE1 Asp/Glu+Glu/Glu (OR = 0.59, 95% CI = 0.42-0.83) genotypes, but not for other XRCC1 variant genotypes. Moreover, there was evidence for a possible gene-gene interaction between XRCC1 and APE1 variants in the association with risk of CM (P = 0.030). We conclude that the APE1 Glu variant may have an effect or interact with XRCC1 in the etiology of CM or in linkage disequilibrium with other untyped protective alleles. Larger studies with more SNPs in the BER genes are needed to verify these findings.

PMID: 16621887 [PubMed - as supplied by publisher]

 

Int J Oncol. 2006 May;28(5):1217-23.

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Association of XRCC1 gene polymorphisms with the susceptibility and chromosomal aberration of testicular germ cell tumors.

Tsuchiya N, Mishina M, Narita S, Kumazawa T, Inoue T, Horikawa Y, Kakinuma H, Yuasa T, Matsuura S, Satoh S, Ogawa O, Habuchi T.

Department of Urology, Akita University School of Medicine, Hondo, Akita 010-8543, Japan.

It is known that many genomic and genetic alterations caused by aging or environmental factors are responsible for cancer development and progression. XRCC1 is involved in the repair of DNA single-strand breaks formed by exposure to ionizing radiation and alkylating agents. The objective of this study was to investigate the association of genomic alterations and the susceptibility of testicular germ cell tumors with XRCC1 polymorphisms. Two polymorphisms of XRCC1, Arg194Trp and Arg399Gln, were genotyped in 83 patients with testicular germ cell tumors (TGCT) and 87 male controls. Allelic imbalances (AI) were evaluated using 4 microsatellite markers in a subgroup of 50 patients. Patients with at least one Gln allele of the Arg399Gln polymorphism had an increased risk of TGCT than those with the Arg/Arg genotype (aOR=1.775, 95% CI=1.045-3.016, P=0.034). Furthermore, the increased risk associated with the Gln allele against the Arg homozygote was more strongly observed in patients with pure seminoma (aOR=2.242, 95% CI=1.149-4.374, P=0.018) or with metastasis (aOR=2.481, 95% CI=1.267-4.862, P=0.008). In the Arg194Trp polymorphism, there was no significant difference in the genotype distribution between TGCT patients and the controls. In AI analysis, the frequency of AI was significantly higher in tumors with at least one Gln allele than those with the Arg/Arg genotype in D13S317 (P=0.010) and in a combination of 4 markers (0.51+/-0.32 vs 0.32+/-28, P=0.028). Our results suggest that the Gln allele of the XRCC1 Arg399Gln polymorphism may genetically modify the development and progression of TGCT through genomic instability.

PMID: 16596238 [PubMed - in process]

Mol Cell. 2006 Mar 17;21(6):837-48.

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Condensin I interacts with the PARP-1-XRCC1 complex and functions in DNA single-strand break repair.

Heale JT, Ball AR Jr, Schmiesing JA, Kim JS, Kong X, Zhou S, Hudson DF, Earnshaw WC, Yokomori K.

Department of Biological Chemistry, School of Medicine, University of California, Irvine, 92697, USA.

Condensins are essential protein complexes critical for mitotic chromosome organization. Little is known about the function of condensins during interphase, particularly in mammalian cells. Here we report the interphase-specific interaction between condensin I and the DNA nick-sensor poly(ADP-ribose) polymerase 1 (PARP-1). We show that the association between condensin I, PARP-1, and the base excision repair (BER) factor XRCC1 increases dramatically upon single-strand break damage (SSB) induction. Damage-specific association of condensin I with the BER factors flap endonuclease 1 (FEN-1) and DNA polymerase delta/epsilon was also observed, suggesting that condensin I is recruited to interact with BER factors at damage sites. Consistent with this, DNA damage rapidly stimulates the chromatin association of PARP-1, condensin I, and XRCC1. Furthermore, depletion of condensin in vivo compromises SSB but not double-strand break (DSB) repair. Our results identify a SSB-specific response of condensin I through PARP-1 and demonstrate a role for condensin in SSB repair.

PMID: 16543152 [PubMed - indexed for MEDLINE]