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TitleStructural basis of RNA polymerase I stalling at UV light-induced DNA damage.
Journal, issue, pagesProc Natl Acad Sci U S A, Vol. 115, Issue 36, Page 8972-8977, Year 2018
Publish dateSep 4, 2018
AuthorsMarta Sanz-Murillo / Jun Xu / Georgiy A Belogurov / Olga Calvo / David Gil-Carton / María Moreno-Morcillo / Dong Wang / Carlos Fernández-Tornero /
PubMed AbstractRNA 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 ...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.
External linksProc Natl Acad Sci U S A / PubMed:30127008 / PubMed Central
MethodsEM (single particle)
Resolution3.6 - 4.6 Å
Structure data

0146

6h67

EMDB-0146, PDB-6h67:
Yeast RNA polymerase I elongation complex stalled by cyclobutane pyrimidine dimer (CPD)
Method: EM (single particle) / Resolution: 3.6 Å

0147

6h68

EMDB-0147, PDB-6h68:
Yeast RNA polymerase I elongation complex stalled by cyclobutane pyrimidine dimer (CPD) with fully-ordered A49
Method: EM (single particle) / Resolution: 4.6 Å

Chemicals

ChemComp-ZN:
Unknown entry

ChemComp-MG:
Unknown entry

Source
  • Saccharomyces cerevisiae S288C (yeast)
  • saccharomyces cerevisiae (brewer's yeast)
  • saccharomyces cerevisiae (strain atcc 204508 / s288c) (yeast)
KeywordsTRANSCRIPTION / RNA Polymerase I / UV-damage / stalling / Cyclobutane Pyrimidine Dimers (CPD)

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