9PVX
RNA polymerase II elongation complex with dA at +1 site, 8-oxo-GTP bound in E-site.
Summary for 9PVX
| Entry DOI | 10.2210/pdb9pvx/pdb |
| Descriptor | RNA, DNA-directed RNA polymerase II subunit RPB9, DNA-directed RNA polymerases I, II, and III subunit RPABC5, ... (16 entities in total) |
| Functional Keywords | rna polymerase ii, oxidative damage, transcription, in vitro transcription, 8-oxoguanine |
| Biological source | Saccharomyces cerevisiae S288C More |
| Total number of polymer chains | 13 |
| Total formula weight | 488059.16 |
| Authors | |
| Primary citation | Hou, P.,Lee, C.,Chong, J.,Oh, J.,Wang, D. Structural basis of transcription-coupled RNA damage by incorporation of oxidized ribonucleotides. Proc.Natl.Acad.Sci.USA, 123:e2602266123-e2602266123, 2026 Cited by PubMed Abstract: Oxidative stress induces damage to DNA, RNA, and nucleotide pools. Unlike well-studied DNA damage, the formation of RNA damage and the impact of an oxidized ribonucleotide pool on transcription fidelity are poorly understood. Here, we investigate the structural basis of transcription-coupled RNA damage and the effect of 8-oxo-guanosine triphosphate (8-oxo-rGTP) on RNA polymerase II (Pol II) transcription fidelity control steps. We revealed that the incorporation efficiency of 8-oxo-rGTP opposite a dC template is comparable to that of GTP. In contrast, the incorporation efficiency of 8-oxo-rGTP opposite a dA template is ~150-fold more efficient than that of GTP. For the extension step, Pol II extends substantially faster from a 3'-8-oxo-rG:dC base pair than from a 3'-8-oxo-rG:dA base pair. For the proofreading step, strikingly, Pol II EC with 3'-8-oxo-rG:dA base pair is much more resistant to backtracking and proofreading than Pol II EC with 3'-8-oxo-rG:dC base pair. Using X-ray crystallography, we revealed that 8-oxo-rGTP adopts different prechemistry binding sites depending on whether it is paired with a dC or a dA template. Upon incorporation, the nucleobase of 8-oxo-rG flips to the -conformation to form a Hoogsteen pair with a dA template, whereas it remains in the -conformation to form a Watson-Crick pair with a dC template. Collectively, our work demonstrates that nucleotide-pool oxidation can directly affect Pol II fidelity control steps and elongation dynamics and induce RNA damage in a transcription-coupled manner. PubMed: 41980106DOI: 10.1073/pnas.2602266123 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (3.39 Å) |
Structure validation
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