The Clash of Macromolecular Titans: Replication-Transcription Conflicts in Bacteria

Abstract

Within the last decade, it has become clear that DNA replication and transcription are routinely in conflict with each other in growing cells. Much of the seminal work on this topic has been carried out in bacteria, specifically, Escherichia coli and Bacillus subtilis; therefore, studies of conflicts in these species deserve special attention. Collectively, the recent findings on conflicts have fundamentally changed the way we think about DNA replication in vivo. Furthermore, new insights on this topic have revealed that the conflicts between replication and transcription significantly influence many key parameters of cellular function, including genome organization, mutagenesis, and evolution of stress response and virulence genes. In this review, we discuss the consequences of replication-transcription conflicts on the life of bacteria and describe some key strategies cells use to resolve them. We put special emphasis on two critical aspects of these encounters: (a) the consequences of conflicts on replisome stability and dynamics, and (b) the resulting increase in spontaneous mutagenesis.

Too Much of a Good Thing: How Ectopic DNA Replication Affects Bacterial Replication Dynamics

“…The co-directionality of highly transcribed genes and DNA replication indicates head-on encounters of replisomes with transcribing RNA polymerase complexes are particularly problematic (French, 1992;Rudolph et al, 2007a;Kim and Jinks-Robertson, 2012;McGlynn et al, 2012;Merrikh et al, 2012), even though any encounter can interfere with ongoing DNA replication (Merrikh et al, 2011;Lang and Merrikh, 2018). Indeed, it was shown in both E. coli and B. subtilis cells that replication of a highly transcribed rrn operon in an orientation opposite to normal caused significant problems (Wang et al, 2007;Boubakri et al, 2010;Srivatsan et al, 2010;De Septenville et al, 2012;Million-Weaver et al, 2015).…”

Does the Semiconservative Nature of DNA Replication Facilitate Coherent Phenotypic Diversity?

“…Another aspect to the importance of replication and the strands in evolution involves the strand-dependent consequences of replication-transcription conflicts, which have been proposed to actually accelerate evolution (27)(28)(29). In the case of the hyperstructure-dependent hypothesis proposed here, it is conceivable that the passage of the replication machinery would destroy a DNA strand-based hyperstructure (30), though the replication machinery may be stalled by encountering even a single RNA polymerase (31). However, the local concentration of the RNA polymerases on and around the transcribed gene could be sufficient to allow resumption of transcription from the strand immediately after the passage of the replication machinery, particularly if transcription has greatly separated the transcribed parental strand from the other untranscribed parental strand (note that differences between the replication of leading and lagging strands might also play a role in the maintenance of a hyperstructure).…”

Macromolecular crowding links ribosomal protein gene dosage to growth rate inVibrio cholerae

“…1a) (4, 5, 7). For instance, essential genes are overrepresented in the replicative leading strand to avoid head-on collisions between the replication and transcription machineries (8). Large inversions occur preferentially symmetrically with respect to the ori-ter axis to avoid the emergence of replichore size imbalance (9, 10).…”