CHAPTER 8: Transcription–Replication Conflicts, Resolution and Coregulation
Published:23 Nov 2021
The processes of genome replication and gene expression take place on the same template, inevitably creating a conflict between these two key cellular machineries. In rapidly growing and dividing bacterial cells, their temporal separation is not possible. The consequences of these conflicts include genome instability and mutagenesis if not cell death, and thus lead to selective pressure to provide a solution. RNA polymerase that has stalled at a DNA damage site or that has backtracked during transcription elongation can constitute a strong roadblock to the replication fork that requires specific cofactors for its prevention or resolution. Moreover, the accumulation of unresolved positive DNA supercoiling ahead of replication and transcription complexes moving towards each other can lead to stalling of both processes. This local change in DNA supercoiling when the conflict occurs in the head-on direction can favour the formation of a stable DNA–RNA double helix behind RNA polymerase, called an R-loop, which can block the passage of the replication fork. Here we describe some of the different mechanisms, requiring the recruitment of specific protein complexes, which can intervene to remove RNA polymerase or reassemble the stalled replication forks.