کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
1981371 1061925 2007 7 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Common XPD (ERCC2) polymorphisms have no measurable effect on nucleotide excision repair and basal transcription
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی زیست شیمی
پیش نمایش صفحه اول مقاله
Common XPD (ERCC2) polymorphisms have no measurable effect on nucleotide excision repair and basal transcription
چکیده انگلیسی

The xeroderma pigmentosum group D (XPD/ERCC2), a subunit of TFIIH, plays a critical role in nucleotide excision repair (NER) and basal transcription. There are hot spots of single nucleotide polymorphism (SNP) within the XPD gene sequence that have been incriminated in the pathophysiology of human cancers, possibly by altering the capacity of the cells for removing DNA damage induced by chemical adducts and UV radiation. A controversy persists on the role of these SNPs and this question has not been approached with appropriate biochemical tests. Thus, we sought to quantify in vitro, the effect of codon variants 201 (p.H201Y), 312 (p.D312N), 751 (p.K751Q) of XPD as well as the double XPD variant (p.D312N/p.K751Q) on NER and basal transcription. We used the baculovirus expression system to reconstitute recombinant TFIIH complexes in which the XPD variants were introduced and we analyzed their specific transcription and NER activities. Experimentally, variations in NER capacity and basal transcription activation of the four variants were not detectable in vitro. Structural analyses of XPD revealed that these single nucleotide polymorphisms sites were located outside the main catalytic domains. Altogether, evolutionary data, structural analyses and biochemical investigations strongly suggest that all XPD variants are comparable regarding the main properties of XPD and TFIIH.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: DNA Repair - Volume 6, Issue 9, 1 September 2007, Pages 1264–1270
نویسندگان
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