Transcription-coupled repair of crosslinking DNA damage

Impediments to faithful transcription must be resolved to ensure accurate gene expression and safeguard normal cellular function. Dedicated DNA repair pathways have therefore evolved to remove transcription-blocking DNA damage, targeted to active genes. Although significant research efforts to date have focussed on the transcription-coupled repair of bulky, UV-induced DNA damage, it is known that other forms of DNA damage can perturb RNA Polymerase II progression. Only in recent years has insight into these pathways emerged, despite the clinical significance of understanding all transcription-coupled repair pathways. These recent observations have highlighted substantial molecular differences in these pathways compared to the canonical UV-damage repair mechanisms. This review summarises our understanding to date of the molecular mechanisms that act to remove both DNA-DNA and DNA-protein crosslinks that block transcription in mammalian cells.