Molecular basis of transcriptional fidelity and DNA lesion-induced transcriptional mutagenesis |
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| Affiliation: | 1. Centre for Cancer Biomarkers CCBIO, Department of Clinical Science, Faculty of Medicine and Dentistry, University of Bergen, Bergen, Norway;2. Department of Biomedicine, Proteomic Unit, Faculty of Medicine and Dentistry, University of Bergen, Bergen, Norway;3. Department of Clinical Science, Leukemia Research Group, Faculty of Medicine and Dentistry, University of Bergen, Bergen, Norway;4. Institute of Nutrition, Directorate of Fisheries, Bergen, Norway;5. Department of Internal Medicine, Hematology Section, Haukeland University Hospital, Bergen, Norway |
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| Abstract: | Maintaining high transcriptional fidelity is essential for life. Some DNA lesions lead to significant changes in transcriptional fidelity. In this review, we will summarize recent progress towards understanding the molecular basis of RNA polymerase II (Pol II) transcriptional fidelity and DNA lesion-induced transcriptional mutagenesis. In particular, we will focus on the three key checkpoint steps of controlling Pol II transcriptional fidelity: insertion (specific nucleotide selection and incorporation), extension (differentiation of RNA transcript extension of a matched over mismatched 3′-RNA terminus), and proofreading (preferential removal of misincorporated nucleotides from the 3′-RNA end). We will also discuss some novel insights into the molecular basis and chemical perspectives of controlling Pol II transcriptional fidelity through structural, computational, and chemical biology approaches. |
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| Keywords: | RNA polymerase II Transcription elongation Fidelity control DNA damage recognition Transcriptional lesion bypass Synthetic nucleotide analogs Unlocked nucleic acid Nonpolar isostere Chemical biology Structural biology Computational biology |
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