Collisions between the replisome and a transcribing RNA polymerase

It is widely reported that DNA replication progression is effected by many factors such as DNA damage, lesion or protein, acid nucleic … , that can lead to fork arrest or sometimes fork collapse. Depending on the situation, cell have different pathways to rescue fork progression or post-replication pathways to faithfully maintain genetic information such as DNA repair ….
In the cell, it’s highly possible that RNA transcription can occur simultaneously with DNA replication. In this case, the collision between replisome and transcription complex is unavoidable. So how does the cell solve this problem?
Depending on gene’s orientation, the replication and transcription can be in the same direction (co-directional) or opposite direction (head-on). Because RNA polymerase also synthesize RNA in 5′ – 3′ direction, therefore in case of co-directional, the collision will occur on leading strand, whereby the leading strand polymerase will hit the end of RNA polymerase. In case of head-on collision mode, the RNA polymerase will meet the helicase on lagging strand.
The detailed molecular basis for this collision is not well known. However, some studies reveal that fork progression is strongly effected when the fork collides with the transcription head-on. In this situation, the fork progression becomes much slower, finally result in fork arrest. This may be due to the appearance of a torsional stress in front of replication fork that makes helicase unable to unwind the duplex DNA. However, co-directional collision of the replisome with RNA polymerase has little or no effect on fork progression. Studies by Richard T. Pomerantz and Mike O’Donnell propose a model for co-directional collision. After hitting a transcription complex, leading strand synthesis is terminated. The RNA polymerase will be pushed from the DNA-RNA junction but the mRNA is retained. The leading strand polymerase hops over the mRNA by remaining bound to the clamp-loader which assembles a new clamp at the 3′ end terminus of the RNA-DNA hybrid. Pol III then binds to the newly assembled clamp and continue chain elongation using the mRNA as the primer. This process leaves behind a gap in the leading strand. The RNA can then be excised and replaced by DNA in a similar repair reaction as occurs during the maturation of Okazaki fragments. Because collision of the lagging strand polymerase with the 5′ terminus of an Okazaki fragment triggers the release of Pol III from the clamp. Thus, the hopping of the leading-strand polymerase proposed in this model may be initiated by a similar collision mechanism.
Figure A. Model of replication bypass of a co-directional RNA polymerase collision. (Richard T. Pomerantz & Mike O’Donnell, Nature 2008)
, The replisome encounters a co-directional RNAP. b, RNAP is displaced from the DNA. The lagging-strand polymerase dissociates from the beta-clamp and DNA but remains bound to the clamp-loader. DnaB remains bound to the lagging strand. c, The clamp-loader assembles a new beta-clamp at the 3′ terminus of the RNA–DNA hybrid. d, The leading-strand polymerase binds to the newly assembled beta-clamp. e, The leading-strand polymerase extends the mRNA leaving behind a nick or gap in the leading strand.
Richard T. Pomerantz & Mike O’Donnell. The replisome uses mRNA as a primer after colliding with RNA polymerase. Nature, 2008.

Ekaterina V. Mirkin and Sergei M. Mirkin. Mechanisms of Transcription-Replication Collisions in Bacteria.Molecular and cellular biology, 2005.

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