Advances in Structural and Single-Molecule Methods for Investigating DNA Lesion Bypass and Repair Polymerases
العنوان: | Advances in Structural and Single-Molecule Methods for Investigating DNA Lesion Bypass and Repair Polymerases |
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المؤلفون: | Austin T. Raper, Zucai Suo, Andrew J. Reed, Varun V. Gadkari |
المصدر: | Chemical Research in Toxicology. 30:260-269 |
بيانات النشر: | American Chemical Society (ACS), 2016. |
سنة النشر: | 2016 |
مصطلحات موضوعية: | 0301 basic medicine, DNA Repair, DNA polymerase, DNA repair, DNA damage, DNA-Directed DNA Polymerase, Crystallography, X-Ray, Toxicology, Article, 03 medical and health sciences, chemistry.chemical_compound, Fluorescence Resonance Energy Transfer, Humans, heterocyclic compounds, Polymerase, 030102 biochemistry & molecular biology, biology, DNA synthesis, General Medicine, Base excision repair, 030104 developmental biology, chemistry, Biochemistry, DNA polymerase IV, biology.protein, DNA, DNA Damage |
الوصف: | Innovative advances in X-ray crystallography and single-molecule biophysics have yielded unprecedented insight into the mechanisms of DNA lesion bypass and damage repair. Time-dependent X-ray crystallography has been successfully applied to view the bypass of 8-oxo-7,8-dihydro-2′-deoxyguanine (8-oxoG), a major oxidative DNA lesion, and the incorporation of the triphosphate form, 8-oxo-dGTP, catalyzed by human DNA polymerase β. Significant findings of these studies are highlighted here, and their contributions to the current mechanistic understanding of mutagenic translesion DNA synthesis (TLS) and base excision repair are discussed. In addition, single-molecule Forster resonance energy transfer (smFRET) techniques have recently been adapted to investigate nucleotide binding and incorporation opposite undamaged dG and 8-oxoG by Sulfolobus solfataricus DNA polymerase IV (Dpo4), a model Y-family DNA polymerase. The mechanistic response of Dpo4 to a DNA lesion and the complex smFRET technique are described here. In this perspective, we also describe how time-dependent X-ray crystallography and smFRET can be used to achieve the spatial and temporal resolutions necessary to answer some of the mechanistic questions that remain in the fields of TLS and DNA damage repair. |
تدمد: | 1520-5010 0893-228X |
URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::3c18cef0cb85141b9c9b730e27448490 https://doi.org/10.1021/acs.chemrestox.6b00342 |
حقوق: | OPEN |
رقم الأكسشن: | edsair.doi.dedup.....3c18cef0cb85141b9c9b730e27448490 |
قاعدة البيانات: | OpenAIRE |
تدمد: | 15205010 0893228X |
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