Transcription-Associated Genome Instability

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. 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. 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.