A1 Refereed original research article in a scientific journal

Structural basis of RNA polymerase I stalling at UV light-induced DNA damage




AuthorsSanz-Murillo M, Xu J, Belogurov GA, Calvo O, Gil-Carton D, Moreno-Morcillo M, Wang D, Fernandez-Tornero C

PublisherNATL ACAD SCIENCES

Publication year2018

JournalProceedings of the National Academy of Sciences of the United States of America

Journal name in sourcePROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

Journal acronymP NATL ACAD SCI USA

Volume115

Issue36

First page 8972

Last page8977

Number of pages6

ISSN0027-8424

eISSN1091-6490

DOIhttps://doi.org/10.1073/pnas.1802626115(external)


Abstract
RNA polymerase I (Pol I) transcribes ribosomal DNA (rDNA) to produce the ribosomal RNA (rRNA) precursor, which accounts for up to 60% of the total transcriptional activity in growing cells. Pol I monitors rDNA integrity and influences cell survival, but little is known about how this enzyme processes UV-induced lesions. We report the electron cryomicroscopy structure of Pol I in an elongation complex containing a cyclobutane pyrimidine dimer (CPD) at a resolution of 3.6 angstrom. The structure shows that the lesion induces an early translocation intermediate exhibiting unique features. The bridge helix residue Arg1015 plays a major role in CPD-induced Pol I stalling, as confirmed by mutational analysis. These results, together with biochemical data presented here, reveal the molecular mechanism of Pol I stalling by CPD lesions, which is distinct from Pol II arrest by CPD lesions. Our findings open the avenue to unravel the molecular mechanisms underlying cell endurance to lesions on rDNA.



Last updated on 2024-26-11 at 11:24