9G2C

Yeast RNA polymerase I elongation complex stalled by an apurinic site, open state

Summary for 9G2C

• Entry DOI: 10.2210/pdb9g2c/pdb
• Related: 9g1v 9g1x 9g23 9g24 9g26 9g27 9g29 9g2b
• EMDB information: 50972
• Descriptor: DNA-directed RNA polymerase I subunit RPA190, DNA-directed RNA polymerases I and III subunit RPAC2, DNA-directed RNA polymerases I, II, and III subunit RPABC4, ... (17 entities in total)
• Functional Keywords: dna lesion, transcription
• Biological source: Saccharomyces cerevisiae (brewer's yeast); More
• Total number of polymer chains: 16
• Total formula weight: 602907.27

Authors

Santos-Aledo, A.,Plaza-Pegueroles, A.,Ruiz, F.M.,Fernandez-Tornero, C. (deposition date: 2024-07-10, release date: 2025-06-18)

Primary citation

Santos-Aledo, A.,Plaza-Pegueroles, A.,Sanz-Murillo, M.,Ruiz, F.M.,Hou, P.,Xu, J.,Gil-Carton, D.,Wang, D.,Fernandez-Tornero, C.
Cryo-EM uncovers a sequential mechanism for RNA polymerase I pausing and stalling at abasic DNA lesions.
Nat Commun, 16:5254-5254, 2025

PubMed Abstract: During synthesis of the ribosomal RNA precursor, RNA polymerase I (Pol I) monitors DNA integrity but its response to DNA damage remains poorly studied. Abasic sites are among the most prevalent DNA lesions in eukaryotic cells, and their detection is critical for cell survival. We report cryo-EM structures of Pol I in different stages of stalling at abasic sites, supported by in vitro transcription studies. Slow nucleotide addition opposite abasic sites occurs through base sandwiching between the RNA 3'-end and the Pol I bridge helix. Templating abasic sites can also cause Pol I cleft opening, which enables the A12 subunit to access the active center. Nucleotide addition opposite the lesion induces a translocation intermediate where DNA bases tilt to form hydrogen bonds with the new RNA base. These findings reveal unique mechanisms of Pol I stalling at abasic sites, differing from arrest by bulky lesions or abasic site handling by RNA polymerase II.

PubMed: 40480971
DOI: 10.1038/s41467-025-60536-4

Experimental method

ELECTRON MICROSCOPY (3.5 Å)