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

Proceedings of the National Academy of Sciences of the United States of America
Wei WangDong Wang

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 structu...Continue Reading

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Citations

Jun 22, 2019·Nucleic Acids Research·Nataliya KitseraAndriy Khobta
May 23, 2020·The Journal of Biological Chemistry·Aleksei AgapovAndrey Kulbachinskiy
Sep 17, 2020·International Journal of Molecular Sciences·Philippe Johann To Berens, Jean Molinier
Apr 15, 2020·Proceedings of the National Academy of Sciences of the United States of America·Juntaek OhDong Wang
Aug 22, 2020·Annual Review of Cell and Developmental Biology·Sara Osman, Patrick Cramer
Dec 4, 2020·Biochimica Et Biophysica Acta. Gene Regulatory Mechanisms·Juntaek OhDong Wang
May 18, 2020·DNA Repair·Petria S Thompson, David Cortez
May 27, 2020·DNA Repair·Amy M WhitakerBret D Freudenthal
Feb 25, 2019·Methods : a Companion to Methods in Enzymology·Juntaek OhDong Wang
Jun 19, 2018·Cell Chemical Biology·Michael D BirnbaumFangliang Zhang
Aug 3, 2019·American Journal of Human Genetics·Vinod Tiwari, David M Wilson
Jan 23, 2019·Biochemical and Biophysical Research Communications·Danil PupovAndrey Kulbachinskiy
Jun 19, 2021·Nature Chemical Biology·Juntaek OhDong Wang
Jun 13, 2018·Biochemistry·Ruixiang WangMarc M Greenberg
Jan 14, 2022·Proceedings of the National Academy of Sciences of the United States of America·Juntaek OhDong Wang

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