Mechanism of Rad26-assisted rescue of stalled RNA polymerase II in transcription-coupled repair

Chunli Yan, Thomas Dodd, Jina Yu, Bernice Leung, Jun Xu, Juntaek Oh, Dong Wang () and Ivaylo Ivanov ()
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Chunli Yan: Georgia State University
Thomas Dodd: Georgia State University
Jina Yu: Georgia State University
Bernice Leung: University of California San Diego
Jun Xu: University of California San Diego
Juntaek Oh: University of California San Diego
Dong Wang: University of California San Diego
Ivaylo Ivanov: Georgia State University

Nature Communications, 2021, vol. 12, issue 1, 1-12

Abstract: Abstract Transcription-coupled repair is essential for the removal of DNA lesions from the transcribed genome. The pathway is initiated by CSB protein binding to stalled RNA polymerase II. Mutations impairing CSB function cause severe genetic disease. Yet, the ATP-dependent mechanism by which CSB powers RNA polymerase to bypass certain lesions while triggering excision of others is incompletely understood. Here we build structural models of RNA polymerase II bound to the yeast CSB ortholog Rad26 in nucleotide-free and bound states. This enables simulations and graph-theoretical analyses to define partitioning of this complex into dynamic communities and delineate how its structural elements function together to remodel DNA. We identify an allosteric pathway coupling motions of the Rad26 ATPase modules to changes in RNA polymerase and DNA to unveil a structural mechanism for CSB-assisted progression past less bulky lesions. Our models allow functional interpretation of the effects of Cockayne syndrome disease mutations.

Date: 2021
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-27295-4

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DOI: 10.1038/s41467-021-27295-4

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