Science · 2007 · 260 citations · 22 references
Life SciencesBiochemistryMolecular BiologyDna RepairNucleic Acid BiochemistryTranscriptionDouble-strand Break RepairNucleotide Excision RepairPolymerase Chain ReactionRna Polymerase FunctionRna Polymerase Ii TranscriptionRna Polymerase StructureBase Damage RecognitionCyclobutane Pyrimidine DimersRna Polymerase Ii StallingTranscription-coupled Direct RepairTranscription-coupled Dna RepairTranslocation MechanismUv-induced Dna Lesion RecognitionUv-induced Dna Lesions
Cells use transcription-coupled repair (TCR) to efficiently eliminate DNA lesions such as ultraviolet light-induced cyclobutane pyrimidine dimers (CPDs). Here we present the structure-based mechanism for the first step in eukaryotic TCR, CPD-induced stalling of RNA polymerase (Pol) II. A CPD in the transcribed strand slowly passes a translocation barrier and enters the polymerase active site. The CPD 5'-thymine then directs uridine misincorporation into messenger RNA, which blocks translocation. Artificial replacement of the uridine by adenosine enables CPD bypass; thus, Pol II stalling requires CPD-directed misincorporation. In the stalled complex, the lesion is inaccessible, and the polymerase conformation is unchanged. This is consistent with nonallosteric recruitment of repair factors and excision of a lesion-containing DNA fragment in the presence of Pol II.
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Structural Basis of Transcription: An RNA Polymerase II Elongation Complex at 3.3 Å Resolution
Averell Gnatt, Patrick Cramer, Jianhua Fu et al. · Science · 2001 · 903 citations · Full text