Molecular and Cellular Biology · 2003 · 145 citations · 34 references
Life SciencesCell BiologyMolecular BiologyDna RepairGene ExpressionTranscriptionDna Damage SignalingDouble-strand Break RepairRna Polymerase RegulationSingle-strand Break RepairTranscription ElongationDna Lesion ProcessingDna Single-strand BreaksProteasomal TurnoverRna Polymerase Ii FunctionSingle-strand Dna BreaksTopoisomerase I-dna Complex RepairTranscription-coupled Dna RepairTranscription-coupled Single-strand Break Repair
Topoisomerase I (Top I)-DNA covalent complexes represent a unique type of DNA lesion whose repair and processing remain unclear. In this study, we show that Top I-DNA covalent complexes transiently arrest RNA transcription in normal nontransformed cells. Arrest of RNA transcription is coupled to activation of proteasomal degradation of Top I and the large subunit of RNA polymerase II. Recovery of transcription occurs gradually and depends on both proteasomal degradation of Top I and functional transcription-coupled repair (TCR). These results suggest that arrest of the RNA polymerase elongation complex by the Top I-DNA covalent complex triggers a 26S proteasome-mediated signaling pathway(s) leading to degradation of both Top I and the large subunit of RNA polymerase II. We propose that proteasomal degradation of Top I and RNA polymerase II precedes repair of the exposed single-strand breaks by TCR.
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