Transcriptional responses to DNA damage (mechanisms and beyond)

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DNA damage interferes with key vital processes, including replication and transcription, which use DNA as a template. Upon a large number of genotoxic impacts, transcription is over-activated and probably results in the activation of various DNA damage recognition processes. During transcription, numerous components of the transcription machinery may act as a platform to recruit repair proteins to the break sites. When DNA damage occurs at a transcribing unit, it leads to a transcriptional block. This multistep process involves various kinases and ubiquitin ligases, including NEDD4 and CUL3, which are involved in the proteasome-dependent degradation of RNA polymerase II (RNAPII) at the site of the damage. Finally, as a result of de novo transcription, ddRNA can be produced at the break site, which recruits the DDR machinery to the lesion sites. Taken together, these results support an uncharacterized function of RNAPII complexes which allows for DNA damage recognition and subsequently, enhances the chance of cell survival following DNA damage.