Transcription-replication encounters, consequences and genomic instability

To ensure replication success, DNA polymerases must negotiate encounters with actively transcribing RNA polymerases that share the genome. This Review highlights the strategies used by prokaryotic and eukaryotic cells to minimize the consequences of collisions between replication forks and transcription complexes to effect faithful DNA replication without compromising gene expression. To ensure accurate duplication of genetic material, the replication fork must overcome numerous natural obstacles on its way, including transcription complexes engaged along the same template. Here we review the various levels of interdependence between transcription and replication processes and how different types of encounters between RNA- and DNA-polymerase complexes may result in clashes of those machineries on the DNA template and thus increase genomic instability. In addition, we summarize strategies evolved in bacteria and eukaryotes to minimize the consequences of collisions, including R-loop formation and topological stresses.