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Structural basis of transcriptional stalling and bypass of abasic DNA lesion by RNA polymerase II.

Wang W, Walmacq C, Chong J, Kashlev M, Wang D
Proc Natl Acad Sci U S A 115 E2538-E2545 (2018)
Related entries: 6blo, 6blp, 6bm2, 6bm4

Cited: 28 times
EuropePMC logo PMID: 29487211

Abstract

Abasic sites are among the most abundant DNA lesions and interfere with DNA replication and transcription, but the mechanism of their action on transcription remains unknown. Here we applied a combined structural and biochemical approach for a comprehensive investigation of how RNA polymerase II (Pol II) processes an abasic site, leading to slow bypass of lesion. Encounter of Pol II with an abasic site involves two consecutive slow steps: insertion of adenine opposite a noninstructive abasic site (the A-rule), followed by extension of the 3'-rAMP with the next cognate nucleotide. Further studies provided structural insights into the A-rule: ATP is slowly incorporated into RNA in the absence of template guidance. Our structure revealed that ATP is bound to the Pol II active site, whereas the abasic site is located at an intermediate state above the Bridge Helix, a conserved structural motif that is cirtical for Pol II activity. The next extension step occurs in a template-dependent manner where a cognate substrate is incorporated, despite at a much slower rate compared with nondamaged template. During the extension step, neither the cognate substrate nor the template base is located at the canonical position, providing a structural explanation as to why this step is as slow as the insertion step. Taken together, our studies provide a comprehensive understanding of Pol II stalling and bypass of the abasic site in the DNA template.

Articles - 6bqf mentioned but not cited (1)

  1. Structural basis of transcriptional stalling and bypass of abasic DNA lesion by RNA polymerase II. Wang W, Walmacq C, Chong J, Kashlev M, Wang D. Proc Natl Acad Sci U S A 115 E2538-E2545 (2018)


Reviews citing this publication (11)

  1. DNA Damage and Associated DNA Repair Defects in Disease and Premature Aging. Tiwari V, Wilson DM. Am J Hum Genet 105 237-257 (2019)
  2. New insights into abasic site repair and tolerance. Thompson PS, Cortez D. DNA Repair (Amst) 90 102866 (2020)
  3. Functions of the major abasic endonuclease (APE1) in cell viability and genotoxin resistance. McNeill DR, Whitaker AM, Stark WJ, Illuzzi JL, McKinnon PJ, Freudenthal BD, Wilson DM. Mutagenesis 35 27-38 (2020)
  4. Structural basis of DNA lesion recognition for eukaryotic transcription-coupled nucleotide excision repair. Wang W, Xu J, Chong J, Wang D. DNA Repair (Amst) 71 43-55 (2018)
  5. Transcription-coupled nucleotide excision repair: New insights revealed by genomic approaches. Duan M, Speer RM, Ulibarri J, Liu KJ, Mao P. DNA Repair (Amst) 103 103126 (2021)
  6. Formation and Recognition of UV-Induced DNA Damage within Genome Complexity. Johann To Berens P, Molinier J. Int J Mol Sci 21 E6689 (2020)
  7. Molecular basis of transcriptional pausing, stalling, and transcription-coupled repair initiation. Oh J, Xu J, Chong J, Wang D. Biochim Biophys Acta Gene Regul Mech 1864 194659 (2021)
  8. RNA polymerase pausing, stalling and bypass during transcription of damaged DNA: from molecular basis to functional consequences. Agapov A, Olina A, Kulbachinskiy A. Nucleic Acids Res 50 3018-3041 (2022)
  9. Transcription fidelity: New paradigms in epigenetic inheritance, genome instability and disease. Bradley CC, Gordon AJE, Halliday JA, Herman C. DNA Repair (Amst) 81 102652 (2019)
  10. Structural and biochemical analysis of DNA lesion-induced RNA polymerase II arrest. Oh J, Xu J, Chong J, Wang D. Methods 159-160 29-34 (2019)
  11. Polymerases and DNA Repair in Neurons: Implications in Neuronal Survival and Neurodegenerative Diseases. Li X, Cao G, Liu X, Tang TS, Guo C, Liu H. Front Cell Neurosci 16 852002 (2022)

Articles citing this publication (16)

  1. RNA polymerase II stalls on oxidative DNA damage via a torsion-latch mechanism involving lone pair-π and CH-π interactions. Oh J, Fleming AM, Xu J, Chong J, Burrows CJ, Wang D. Proc Natl Acad Sci U S A 117 9338-9348 (2020)
  2. Nucleotide excision repair of abasic DNA lesions. Kitsera N, Rodriguez-Alvarez M, Emmert S, Carell T, Khobta A. Nucleic Acids Res 47 8537-8547 (2019)
  3. Rotational Effects within Nucleosome Core Particles on Abasic Site Reactivity. Wang R, Yang K, Banerjee S, Greenberg MM. Biochemistry 57 3945-3952 (2018)
  4. Stacking-induced fluorescence increase reveals allosteric interactions through DNA. Morten MJ, Lopez SG, Steinmark IE, Rafferty A, Magennis SW. Nucleic Acids Res 46 11618-11626 (2018)
  5. Molecular and structural characterization of disease-associated APE1 polymorphisms. Whitaker AM, Stark WJ, Flynn TS, Freudenthal BD. DNA Repair (Amst) 91-92 102867 (2020)
  6. 8-Oxo-guanine DNA damage induces transcription errors by escaping two distinct fidelity control checkpoints of RNA polymerase II. Konovalov KA, Pardo-Avila F, Tse CKM, Oh J, Wang D, Huang X. J Biol Chem 294 4924-4933 (2019)
  7. Transcriptional processing of an unnatural base pair by eukaryotic RNA polymerase II. Oh J, Shin J, Unarta IC, Wang W, Feldman AW, Karadeema RJ, Xu L, Xu J, Chong J, Krishnamurthy R, Huang X, Romesberg FE, Wang D. Nat Chem Biol 17 906-914 (2021)
  8. Human TDP1, APE1 and TREX1 repair 3'-DNA-peptide/protein cross-links arising from abasic sites in vitro. Wei X, Wang Z, Hinson C, Yang K. Nucleic Acids Res 50 3638-3657 (2022)
  9. Conserved Trigger Loop Histidine of RNA Polymerase II Functions as a Positional Catalyst Primarily through Steric Effects. Palo MZ, Zhu J, Mishanina TV, Landick R. Biochemistry 60 3323-3336 (2021)
  10. A Rapid and Precise Mutation-Activated Fluorescence Reporter for Analyzing Acute Mutagenesis Frequency. Birnbaum MD, Nemzow L, Kumar A, Gong F, Zhang F. Cell Chem Biol 25 1038-1049.e5 (2018)
  11. RNA polymerase II trapped on a molecular treadmill: Structural basis of persistent transcriptional arrest by a minor groove DNA binder. Oh J, Jia T, Xu J, Chong J, Dervan PB, Wang D. Proc Natl Acad Sci U S A 119 e2114065119 (2022)
  12. Molecular insight into how the position of an abasic site modifies DNA duplex stability and dynamics. Ashwood B, Jones MS, Lee Y, Sachleben JR, Ferguson AL, Tokmakoff A. Biophys J 123 118-133 (2024)
  13. Role of the trigger loop in translesion RNA synthesis by bacterial RNA polymerase. Agapov A, Ignatov A, Turtola M, Belogurov G, Esyunina D, Kulbachinskiy A. J Biol Chem 295 9583-9595 (2020)
  14. Back-Up Base Excision DNA Repair in Human Cells Deficient in the Major AP Endonuclease, APE1. Kim DV, Diatlova EA, Zharkov TD, Melentyev VS, Yudkina AV, Endutkin AV, Zharkov DO. Int J Mol Sci 25 64 (2023)
  15. Genome-wide maps of UVA and UVB mutagenesis in yeast reveal distinct causative lesions and mutational strand asymmetries. Laughery MF, Plummer DA, Wilson HE, Vandenberg BN, Mitchell D, Mieczkowski PA, Roberts SA, Wyrick JJ. Genetics 224 iyad086 (2023)
  16. Visualizing the coordination of apurinic/apyrimidinic endonuclease (APE1) and DNA polymerase β during base excision repair. Fairlamb MS, Spies M, Washington MT, Freudenthal BD. J Biol Chem 299 104636 (2023)


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