RNA polymerase between lesion bypass and DNA repair.

DNA damage leads to heritable changes in the genome via DNA replication. However, as the DNA helix is the site of numerous other transactions, notably transcription, DNA damage can have diverse repercussions on cellular physiology. In particular, DNA lesions have distinct effects on the passage of transcribing RNA polymerases, from easy bypass to almost complete block of transcription elongation. The fate of the RNA polymerase positioned at a lesion is largely determined by whether the lesion is structurally subtle and can be accommodated and eventually bypassed, or bulky, structurally distorting and requiring remodeling/complete dissociation of the transcription elongation complex, excision, and repair. Here we review cellular responses to DNA damage that involve RNA polymerases with a focus on bacterial transcription-coupled nucleotide excision repair and lesion bypass via transcriptional mutagenesis. Emphasis is placed on the explosion of new structural information on RNA polymerases and relevant DNA repair factors and the mechanistic models derived from it.