Showing papers by "Houra Merrikh published in 2019"
TL;DR: It is suggested that AMR development can be inhibited through inactivation of evolvability factors (potentially with “anti-evolution” drugs)—in particular, Mfd—providing an unexplored route toward battling the AMR crisis.
138 citations
TL;DR: It is found that head-on conflict resolution requires the relaxation of positive supercoils by type II topoisomerases, DNA gyrase and Topo IV, and it is suggested that gyrases plays a fundamental role in the evolution of head- on genes.
Abstract: Conflicts between replication and transcription machineries have profound effects on chromosome duplication, genome organization, as well as evolution across species. Head-on conflicts (lagging strand genes) are significantly more detrimental than co-directional conflicts (leading strand genes). The source of this fundamental difference is unknown. Here, we report that topological stress underlies this difference. We find that head-on conflict resolution requires the relaxation of positive supercoils by type II topoisomerases, DNA gyrase and Topo IV. Interestingly, we find that after positive supercoil resolution gyrase also introduces excessive negative supercoils at head-on conflict regions, driving pervasive R-loop formation. The formation of these R-Loops through gyrase activity is most likely caused by the diffusion of excessive negative supercoils through RNA polymerase spinning. Altogether, these results provide critical mechanistic insights into head-on replication-transcription conflicts and suggest that gyrase plays a fundamental role in the evolution of head-on genes.
11 citations
TL;DR: The different physical states of RNAP during transcription are discussed, and how each distinct state can influence conflict severity and potentially trigger the involvement of Mfd are proposed.
9 citations