Transcription is one of the main molecular processes of life since it converts genomic information into RNA molecules that can either exert their function directly or be translated into proteins. Prokaryotes and eukaryotes differ in many aspects, the most relevant being that transcription and translation occur concomitantly in prokaryotes, whereas eukaryotic transcripts need to be exported from the cell nucleus to the cytoplasm for translation and that eukaryotic genomes are packaged into chromatin. Additionally, prokaryotes have a single RNA polymerase (RNAP) holoenzyme, whereas eukaryotes possess three nuclear RNAPs. Specific differences between prokaryotes and eukaryotes are determined by the nuclear structure of the latter, the basic features of transcription being conserved. Transcription can be divided into three functional steps initiation, elongation, and termination all of which are tightly controlled to ensure appropriate gene expression. During transcription, the two complementary DNA strands are transiently separated to allow the transcription polymerase to copy one of the strands into RNA. In the transcription bubble, located within the RNAP, the transcribed DNA strand (or template strand, TS) is paired with∼ 9 nucleotides of RNA while the nontranscribed strand (or nontemplate strand, NTS) remains unpaired. Part of the unpaired NTS runs along the RNAP, thus being more exposed than the remainder of the DNA forming the transcription bubble. 1 In addition, transcription elongation is not a uniform and independent process since it is associated with changes in local DNA supercoiling and chromatin remodeling and occurs in coordination with mRNA processing and export in eukaryotes or with translation in prokaryotes. Thus, as the RNAP moves forward through the DNA template it can undergo pauses and backward motions of a few nucleotides. 2

Strikingly, transcription not only plays a key cellular role as the first step in gene expression but also affects other DNA transactions. Increasing evidence in the last three decades has shown that transcription is an important source of genetic variability. Transcription enhances the rate of mutations and recombination, the major cellular processes generating variability. Mutations and recombination stimulated by transcription are termed transcription-associated mutation (TAM) and transcription-associated recombination (TAR), respectively. Together they are referred to as transcription-associated genome instability (TAGIN). Mutagenesis mainly occurs during replication, either as mistakes introduced by DNA polymerase when copying an undamaged template or as errors