The Impact of Minor-Groove N2-Alkyl-2′-deoxyguanosine Lesions on DNA Replication in Human Cells
| العنوان: | The Impact of Minor-Groove N2-Alkyl-2′-deoxyguanosine Lesions on DNA Replication in Human Cells |
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| المؤلفون: | Nathan E. Price, Jun Wu, Hua Du, Xiaochuan Liu, Lin Li, Yinsheng Wang |
| المصدر: | ACS Chemical Biology. 14:1708-1716 |
| بيانات النشر: | American Chemical Society (ACS), 2019. |
| سنة النشر: | 2019 |
| مصطلحات موضوعية: | 0301 basic medicine, biology, 010405 organic chemistry, Chemistry, Guanine, DNA replication, General Medicine, 01 natural sciences, Biochemistry, Molecular biology, 0104 chemical sciences, 03 medical and health sciences, chemistry.chemical_compound, 030104 developmental biology, Shuttle vector, biology.protein, Molecular Medicine, Deoxyguanosine, REV1, Transversion, Polymerase, DNA |
| الوصف: | Endogenous metabolites and exogenous chemicals can induce covalent modifications on DNA, producing DNA lesions. The N2 of guanine was shown to be a common alkylation site in DNA; however, not much is known about the influence of the size of the alkyl group in N2-alkyldG lesions on cellular DNA replication or how translesion synthesis (TLS) polymerases modulate DNA replication past these lesions in human cells. To answer these questions, we employ a robust shuttle vector method to investigate the impact of four N2-alkyldG lesions (i.e., with the alkyl group being a methyl, ethyl, n-propyl, or n-butyl group) on DNA replication in human cells. We find that replication through the N2-alkyldG lesions was highly efficient and accurate in HEK293T cells or isogenic CRISPR-engineered cells with deficiency in polymerase (Pol) ζ or Pol η. Genetic ablation of Pol ι, Pol κ, or Rev1, however, results in decreased bypass efficiencies and elicits substantial frequencies of G → A transition and G → T transversion mutation... |
| تدمد: | 1554-8937 1554-8929 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_________::227f42344b0386f3ae6dfc687ac30e96 https://doi.org/10.1021/acschembio.9b00129 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi...........227f42344b0386f3ae6dfc687ac30e96 |
| قاعدة البيانات: | OpenAIRE |
Find this issue from the American Chemical Society | تدمد: | 15548937 15548929 |
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