Molecular Mechanisms of Transcription-Coupled Repair

Transcription-coupled repair (TCR), discovered as preferential nucleotide excision repair of UV-induced cyclobutane pyrimidine dimers located in transcribed mammalian genes compared to those in nontranscribed regions of the genome, is defined as faster repair of the transcribed strand versus the nontranscribed strand in transcribed genes. The phenomenon, universal in model organisms including Escherichia coli, yeast, Arabidopsis, mice, and humans, involves a translocase that interacts with both RNA polymerase stalled at damage in the transcribed strand and nucleotide excision repair proteins to accelerate repair. Drosophila, a notable exception, exhibits TCR but lacks an obvious TCR translocase. Mutations inactivating TCR genes cause increased damage-induced mutagenesis in E. coli and severe neurological and UV sensitivity syndromes in humans. To date, only E. coli TCR has been reconstituted in vitro with purified proteins. Detailed investigations of TCR using genome-wide next-generation sequencing methods, cryo-electron microscopy, single-molecule analysis, and other approaches have revealed fascinating mechanisms.

Automated summary

Transcription-coupled repair (TCR) is a phenomenon in which UV-induced cyclobutane pyrimidine dimers are preferentially repaired in transcribed genes compared to nontranscribed regions. TCR involves a translocase that interacts with RNA polymerase and repair proteins to accelerate the repair process. This phenomenon is universal in model organisms but Drosophila is an exception, as it exhibits TCR without an obvious translocase. Mutations in TCR genes can lead to increased damage-induced mutagenesis and UV sensitivity syndromes. So far, only E. coli TCR has been successfully reconstituted in vitro.