The role of transcription elongation factor IIS in transcription-coupled nucleotide excision repair

Abstract

Transcription-coupled nucleotide excision repair (TC-NER) removes bulky DNA lesions from the template strand at actively transcribed genes. The RNA polymerase II (RNAPII) holoenzyme complex forms a stable ternary complex at the site of DNA damage which may block access of DNA repair proteins to the site of DNA lesions. Therefore, there is considerable interest in understanding how repair is coupled to transcription. Based on elegant in vitro studies, it has been hypothesized that transcription elongation factor IIS (TFIIS), by catalyzing the reverse translocation of RNAPII, may allow access of DNA repair proteins to sites of DNA damage. Here, we tested this hypothesis by assessing TC-NER capacity in cells in which TFIIS expression has been reduced by RNA interference. Surprisingly, we found that decreased TFIIS levels did not affect the repair of transcription-blocking DNA lesions and did not affect the sensitivity of targeted cells to UV light or cisplatin. These results do not support a role for TFIIS in TC-NER. We conclude conservatively that TFIIS levels are not limiting for TC-NER.