Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
10823390 | DNA Repair | 2012 | 9 Pages |
Abstract
⺠R257L and R103Q, the two variants of NEIL2, predominantly present in patients with squamous cell lung carcinoma, are linked and inherited together in the population. ⺠R257L shows only a modest decrease (â¼1.5-fold) in DNA glycosylase activity; however, the total BER activity is significantly decreased (â¼5-fold) compared to the wild type enzyme. ⺠Decreased interaction of the R257L variant with downstream proteins in the BER pathway, particularly with DNA polymerase β, contributes to reduced repair. ⺠R257L-expressing cells accumulate significant amounts of endogenous DNA damage. ⺠Depletion of NEIL2 in Chinese hamster lung V79 cells induced higher spontaneous mutation frequency, indicating the role of NEIL2 in repairing endogenous, oxidative genome damage.
Keywords
RNAPIIHprtOGG16-TG6-thioguanineFPGXRCC1Nth1BERRFLPNEIL2MAFImmunocomplexX-Ray Repair Cross-Complementing Protein 1PLAPNKPUTRRNA polymerase IIapurinic/apyrimidinic sitePolβSSBsProximity ligation assaySCLCbase excision repairAP siteLung cancerNSCLCsingle-strand breaksminor allele frequencyuntranslated regionodd ratiowild typehypoxanthine phosphoribosyltransferaserestriction fragment length polymorphismpolymerase βSingle nucleotide polymorphismSNPnon-small-cell lung carcinomaSmall-cell lung carcinoma
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Authors
Sanjib Dey, Amit K. Maiti, Muralidhar L. Hegde, Pavana M. Hegde, Istvan Boldogh, Partha S. Sarkar, Sherif Z. Abdel-Rahman, Altaf H. Sarker, Bo Hang, Jingwu Xie, Alan E. Tomkinson, Mian Zhou, Binghui Shen, Guanghai Wang, Chen Wu, Dianke Yu, Dongxin Lin,