Intersections between transcription-coupled repair and alkylation damage reversal |
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| Affiliation: | 1. Department of Biochemistry, University of Colorado Boulder, Boulder, CO, 80309, USA;2. Howard Hughes Medical Institute, University of Colorado Boulder, Boulder, CO, 80309, USA;1. Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, 77030, USA;2. Medical Scientist Training Program, Baylor College of Medicine, Houston, TX, 77030, USA;3. Robert and Janice McNair Foundation/ McNair Medical Institute M.D./Ph.D. Scholars Program, Baylor College of Medicine, Houston, TX, 77030, USA;4. Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, TX, 77030, USA;5. Dan L. Duncan Cancer Center, Baylor College of Medicine, Houston, TX, 77030, USA;1. Laboratory of Molecular Biology, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, 9000 Rockville Pike, Bethesda, MD, 20892, USA;2. Laboratory of Molecular Gerontology, National Institute of Aging, National Institutes of Health, 251 Bayview Blvd, Baltimore, MD, 21224, USA;3. Department of Therapeutic Radiology, Yale University, New Haven, CT, 06520-8040, USA;1. Department of Pharmacological Sciences, State University of New York at Stony Brook, Stony Brook, New York, 11794, USA;2. Biochemistry and Structural Biology graduate program, Stony Brook University, New York 11794, USA;3. Stony Brook Cancer Center, Renaissance School of Medicine at Stony Brook University, Stony Brook, New York, 11794, USA |
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| Abstract: | The response to DNA damage intersects with many other physiological processes in the cell, such as DNA replication, chromatin remodeling, and the cell cycle. Certain damaging lesions, such as UV-induced pyrimidine dimers, also strongly block RNA polymerases, necessitating the coordination of the repair mechanism with remodeling of the elongating transcriptional machinery, in a process called transcription-coupled nucleotide excision repair (TC-NER). This pathway is typically not thought to be engaged with smaller lesions such as base alkylation. However, recent work has uncovered the potential for shared molecular components between the cellular response to alkylation and UV damage. Here, we review our current understanding of the alkylation damage response and its impacts on RNA biogenesis. We give particular attention to the Activating Signal Cointegrator Complex (ASCC), which plays important roles in the transcriptional response during UV damage as well as alkylation damage reversal, and intersects with trichothiodystrophy, an inherited disease associated with TC-NER. |
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| Keywords: | Alkylation AlkB ASCC DNA damage Nucleotide excision repair RNF113A Transcription Trichothiodystrophy |
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