Bypass of complex co-directional replication-transcription collisions by replisome skipping

Collisions between the replisome and RNA polymerases [RNAP(s)] are the main obstacle to DNA replication. These collisions can occur either head-on or co-directionally with respect to the direction of translocation of both complexes. Whereas head-on collisions require additional factors to be resolved, co-directional collisions are thought to be overcome by the replisome itself using the mRNA transcript as a primer. We show that mRNA takeover is utilized primarily after collisions with single RNAP complexes with short transcripts. Bypass of more complex transcription complexes requires the synthesis of a new primer downstream of the RNAP for the replisome to resume leading-strand synthesis. In both cases, bypass proceeds with displacement of the RNAP. Rep, Mfd, UvrD and RNase H can process the RNAP block and facilitate replisome bypass by promoting the formation of continuous leading strands. Bypass of co-directional RNAP(s) and/or R-loops is determined largely by the length of the obstacle that the replisome needs to traverse: R-loops are about equally as potent obstacles as RNAP arrays if they occupy the same length of the DNA template.

Automated summary

Collisions between the replisome and RNA polymerases are the main obstacle to DNA replication. Utilization of mRNA transcripts as primers helps overcome co-directional collisions. The process involves synthesizing new primers downstream of the RNA polymerases to facilitate leading-strand synthesis during bypass.