6H67

Yeast RNA polymerase I elongation complex stalled by cyclobutane pyrimidine dimer (CPD)

Summary for 6H67

• Entry DOI: 10.2210/pdb6h67/pdb
• EMDB information: 0146
• Descriptor: DNA-directed RNA polymerase I subunit RPA190, DNA-directed RNA polymerases I, II, and III subunit RPABC5, DNA-directed RNA polymerases I and III subunit RPAC2, ... (19 entities in total)
• Functional Keywords: rna polymerase i, uv-damage, stalling, cyclobutane pyrimidine dimers (cpd), transcription
• Biological source: Saccharomyces cerevisiae (strain ATCC 204508 / S288c); More
• Total number of polymer chains: 17
• Total formula weight: 625814.71

Authors

Sanz-Murillo, M.,Xu, J.,Gil-Carton, D.,Wang, D.,Fernandez-Tornero, C. (deposition date: 2018-07-26, release date: 2018-08-29, Last modification date: 2024-05-15)

Primary citation

Sanz-Murillo, M.,Xu, J.,Belogurov, G.A.,Calvo, O.,Gil-Carton, D.,Moreno-Morcillo, M.,Wang, D.,Fernandez-Tornero, C.
Structural basis of RNA polymerase I stalling at UV light-induced DNA damage.
Proc. Natl. Acad. Sci. U.S.A., 115:8972-8977, 2018

PubMed 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 Å. 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.

PubMed: 30127008
DOI: 10.1073/pnas.1802626115

Experimental method

ELECTRON MICROSCOPY (3.6 Å)