Common XPD (ERCC2) polymorphisms have no measurable effect on nucleotide excision repair and basal transcription

Lainé, Jean; Mocquet, Vincent; Bonfanti, Marion; Braun, Cathy; Egly, Jean Marc; Brousset, Pierre

doi:10.1016/j.dnarep.2007.02.010

Cited by 49 publications

(29 citation statements)

References 28 publications

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“…Obviously, sequence variations at codon 312 and codon 751 do not alter the cellular capacity for DNA repair. This conclusion is supported by studies of Laine et al (2007) who applied recombinant TFIIH complexes containing the XPD variants 312Asn or 751Gln in in vitro assays to directly investigate the effect of these variants on DNA repair and basal transcription. Compared to wild-type XPD, variants 312Asn or 751Gln did not show significant differences neither for their repair nor for their transcriptional activities in vitro, which is a strong indication that the two XPD SNPs at codon 312 and codon 751 do not affect the function of the protein.…”

Section: Common Snps In the Xpd Genesupporting

confidence: 53%

Single nucleotide polymorphisms in DNA repair genes and putative cancer risk

et al. 2016

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Single nucleotide polymorphisms (SNPs) are the most frequent type of genetic alterations between individuals. An SNP located within the coding sequence of a gene may lead to an amino acid substitution and in turn might alter protein function. Such a change in protein sequence could be functionally relevant and therefore might be associated with susceptibility to human diseases, such as cancer. DNA repair mechanisms are known to play an important role in cancer development, as shown in various human cancer syndromes, which arise due to mutations in DNA repair genes. This leads to the question whether subtle genetic changes such as SNPs in DNA repair genes may contribute to cancer susceptibility. In numerous epidemiological studies, efforts have been made to associate specific SNPs in DNA repair genes with altered DNA repair and cancer. The present review describes some of the common and most extensively studied SNPs in DNA repair genes and discusses whether they are functionally relevant and subsequently increase the likelihood that cancer will develop.

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Section: Common Snps In the Xpd Genesupporting

confidence: 53%

Single nucleotide polymorphisms in DNA repair genes and putative cancer risk

et al. 2016

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“…It is involved in separating the double helix at lesion sites in the nucleotide excision repair pathway (NER), and causes Xeroderma Pigmentosum when mutated in the germ line [1]. ERCC2 is a component of the transcription factor complex, TFIIH, which participates in both NER and basal transcription [2]. Several polymorphisms have been identified in the coding region of ERCC2, whereas the two commonly occurring, Asp312Asn and Lys751Gln, have been studied most extensively [3].…”

Section: Introductionmentioning

confidence: 99%

Meta-analysis of two ERCC2 (XPD) polymorphisms, Asp312Asn and Lys751Gln, in breast cancer

Pabalan

Francisco-Pabalan

Sung

et al. 2010

Breast Cancer Res Treat

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The excision repair cross-complementing group 2 gene (ERCC2) plays a key role in DNA repair. Several polymorphisms in the ERCC2 gene have been described, including the commonly occurring Lys751Gln and Asp312Asn polymorphisms. Studies investigating the association of these polymorphisms with breast cancer risk produced controversial results. To evaluate these associations presented in diverse populations, we have conducted a meta-analysis based on 40 studies from 33 publications in PubMed which included analyses of Lys751Gln (14,545 cases, 15,352 controls) and Asp312Asn polymorphisms (16,254 cases, 14,006 controls). Overall findings of both polymorphisms have implicated null effects (OR = 1.01-1.03) when the analyses were limited to the statistically powerful (≥80%) studies. Although modestly increased statistically significant breast cancer risk was detected in the underpowered studies (≤80%), removal of outliers resulted in null associations. Ethnic stratification showed non-significant and relatively null associations for both polymorphisms with breast cancer risk for the overall Caucasians as well as North American and the European sub-populations. Although statistically increased and decreased risks were observed for the homogenous populations of African-Americans (Lys751Gln, OR 1.25, 95% CI 1.03-1.53, P = 0.03) and Asians (Asp312Asn, ORs: 0.53-0.55, P values: 0.02-0.03), respectively, this may be the result of small sample size. Analyses of the homogeneous adduct studies, with relatively large sample size, exhibited increased risk for Lys751Gln (OR 1.20, 95% CI (1.02-1.41), P = 0.03) and Asp312Asn (OR 1.17 95% CI 1.02-1.34, P = 0.03) under the dominant genetic model. In conclusion, our results suggest null associations of both polymorphisms in the overall and the Caucasian subgroups, although some effects can be suggested for relatively smaller minority studies. Increased risk effect was more visible when the adduct studies are considered, suggesting the role of these polymorphisms in the presence of exposure to DNA damaging agents.

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“…The XPD protein is involved in transcription-coupled NER and is an integral member of the basal transcription factor BTF2/TFIIH complex. The XPD gene product has an ATP-dependent DNA helicase activity and belongs to the RAD3/ XPD subfamily of helicases (4). Mutations in the XPD gene can result in three different disorders: xeroderma pigmentosum, trichothiodystrophy, and Cockayne syndrome (5).…”

Section: Introductionmentioning

confidence: 99%