کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
3299305 | 1209926 | 2008 | 10 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Characterization of Mutant MUTYH Proteins Associated With Familial Colorectal Cancer
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کلمات کلیدی
BER8-hydroxyguanineROS - ROSbase excision repair - تعمیر پایه پایهColorectal cancer - سرطان روده بزرگmap - نقشهwild type - نوع وحشیSingle-nucleotide polymorphism - پلی مورفیسم تک نوکلئوتیدیMUTYH-associated polyposis - پولیپوز وابسته به MUTYHSNP - چندریختی تک-نوکلئوتیدCRC - کد افزونگی دورهای Reactive oxygen species - گونههای فعال اکسیژن
موضوعات مرتبط
علوم پزشکی و سلامت
پزشکی و دندانپزشکی
بیماریهای گوارشی
پیش نمایش صفحه اول مقاله
چکیده انگلیسی
Background & Aims: The human mutyh gene encodes a base excision repair protein that prevents G:C to T:A transversions in DNA. Biallelic mutations in this gene are associated with recessively inherited familial colorectal cancer. The aim of this study was to characterize the functional activity of mutant-MUTYH and single-nucleotide polymorphism (SNP)-MUTYH proteins involving familial colorectal cancer. Methods: MUTYH variants were cloned and assayed for their glycosylase and DNA binding activities using synthetic double-stranded oligonucleotide substrates by analyzing cleavage products by polyacrylamide gel electrophoresis. Results: In this study, we have characterized 9 missense/frameshift mutants and 2 SNPs for their DNA binding and repair activity in vitro. Two missense mutants (R260Q and G382D) were found to be partially active in both glycosylase and DNA binding, whereas 3 other missense mutants (Y165C, R231H, and P281L) were severely defective in both activities. All of the frameshift mutants (Y90X, Q377X, E466X, and 1103delC) were completely devoid of both glycosylase and DNA binding activities. One SNP (V22M) showed the same activity as wild-type MUTYH protein, but the other SNP (Q324H) was partially impaired in adenine removal. Conclusions: This study of MUTYH mutants suggests that certain SNPs may be as partially dysfunctional in base excision repair as missense-MUTYH mutants and lead to colorectal carcinogenesis.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Gastroenterology - Volume 135, Issue 2, August 2008, Pages 499-507.e1
Journal: Gastroenterology - Volume 135, Issue 2, August 2008, Pages 499-507.e1
نویسندگان
Mohsin Ali, Hyeja Kim, Sean Cleary, Claire Cupples, Steven Gallinger, Robert Bristow,