Mechanism of Rad26-assisted rescue of stalled RNA polymerase II in transcription-coupled repair
Autor: | Bernice Leung, Thomas Dodd, Chunli Yan, Jun Xu, Ivaylo Ivanov, Dong Wang, Juntaek Oh, Jina Yu |
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Jazyk: | angličtina |
Rok vydání: | 2021 |
Předmět: |
Models
Molecular musculoskeletal diseases congenital hereditary and neonatal diseases and abnormalities DNA Repair Science Allosteric regulation General Physics and Astronomy RNA polymerase II Biology Genome General Biochemistry Genetics and Molecular Biology Cockayne syndrome Article chemistry.chemical_compound Computational biophysics RNA polymerase medicine Humans Protein Interaction Domains and Motifs Cockayne Syndrome Poly-ADP-Ribose Binding Proteins Adenosine Triphosphatases Multidisciplinary Cryoelectron Microscopy DNA Helicases Computational Biology nutritional and metabolic diseases General Chemistry DNA medicine.disease Cell biology Nucleotide excision repair DNA Repair Enzymes chemistry Mutation biology.protein RNA Polymerase II Molecular modelling Function (biology) |
Zdroj: | Nature Communications, Vol 12, Iss 1, Pp 1-12 (2021) Nature Communications |
ISSN: | 2041-1723 |
Popis: | 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. Here the authors provide models of RNA polymerase II bound to the yeast CSB ortholog Rad26 in different nucleotide states; explain how Rad26 domain motions help the polymerase progress past DNA lesions; and interpret the effects of CSB-associated disease mutations. |
Databáze: | OpenAIRE |
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