Transcription-coupled DNA repair without the transcription-coupling repair factor

摘要

Repair of DNA damage by the versatile nucleotide excision repair (NER) pathway proceeds much faster in the transcribed strand of an active gene than it does in the non-transcribed strand or in the global genome. This transcription-coupled repair (TCR) was first described almost 15 years ago but, despite its obvious importance for maintenance of genome integrity, little has been learned about the molecular mechanisms that make such preferential repair possible. New results from the Brouwer laboratory now suggest that TCR works better when the efficiency of transcriptional elongation is relaxed. Two genes, Cockayne's Syndrome A (CSA) and B (CSB), encode proteins that are involved in this process. The yeast homologue of CSB is RAD26and, like mammalian CS cells, rad26cells show a markedly slower repair of the transcribed strand of an active gene than do normal cells. CSB and Rad26 are DNA-dependent ATPases often thought of as possible functional analogues of the bacterial transcription coupling repair factor (TCRF) protein, which interacts directly with the bacterial NER machinery and is capable of displacing a stalled RNA polymerase, thus enabling DNA repair.