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TitleMechanism of translesion transcription by RNA polymerase II and its role in cellular resistance to DNA damage.
Journal, issue, pagesMol Cell, Vol. 46, Issue 1, Page 18-29, Year 2012
Publish dateApr 13, 2012
AuthorsCeline Walmacq / Alan C M Cheung / Maria L Kireeva / Lucyna Lubkowska / Chengcheng Ye / Deanna Gotte / Jeffrey N Strathern / Thomas Carell / Patrick Cramer / Mikhail Kashlev /
PubMed AbstractUV-induced cyclobutane pyrimidine dimers (CPDs) in the template DNA strand stall transcription elongation by RNA polymerase II (Pol II). If the nucleotide excision repair machinery does not promptly ...UV-induced cyclobutane pyrimidine dimers (CPDs) in the template DNA strand stall transcription elongation by RNA polymerase II (Pol II). If the nucleotide excision repair machinery does not promptly remove the CPDs, stalled Pol II creates a roadblock for DNA replication and subsequent rounds of transcription. Here we present evidence that Pol II has an intrinsic capacity for translesion synthesis (TLS) that enables bypass of the CPD with or without repair. Translesion synthesis depends on the trigger loop and bridge helix, the two flexible regions of the Pol II subunit Rpb1 that participate in substrate binding, catalysis, and translocation. Substitutions in Rpb1 that promote lesion bypass in vitro increase UV resistance in vivo, and substitutions that inhibit lesion bypass decrease cell survival after UV irradiation. Thus, translesion transcription becomes essential for cell survival upon accumulation of the unrepaired CPD lesions in genomic DNA.
External linksMol Cell / PubMed:22405652 / PubMed Central
MethodsX-ray diffraction
Resolution3.4 Å
Structure data

PDB-4a93:
RNA Polymerase II elongation complex containing a CPD Lesion
Method: X-RAY DIFFRACTION / Resolution: 3.4 Å

Chemicals

ChemComp-ZN:
Unknown entry

ChemComp-MG:
Unknown entry

Source
  • saccharomyces cerevisiae (brewer's yeast)
KeywordsTRANSCRIPTION / TRANSCRIPTION FIDELITY / TRANSCRIPTION COUPLED DNA REPAIR / DNA DAMAGE / DNA REPAIR / PYRIMIDINE DIMERS

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