Termination of DNA Replication in Prokaryotes

Abstract

Most bacteria and archaea have circular chromosomes, in which DNA replication begins at a site known as an origin of replication. Double-stranded DNA unwound at the origin creates two replication forks that are engaged by DNA polymerase complexes (replisomes) that advance each fork and proceed in 21 opposite directions away from the origin, copying the original strands. Termination of DNA replication 22 occurs when the two forks meet and fuse, creating two separate double-stranded DNA molecules. In 23 the well-studied bacteria Escherichia coli and Bacillus subtilis, this occurs in the terminus region, which is situated diametrically opposite the origin. Failure to terminate chromosome replication correctly can lead to problems with genome function and stability, including DNA over-replication. In contrast, some 26 archaea have multi-origin chromosomes and do not appear to specifically regulate the location of termination.

Interplay between chromosomal architecture and termination of DNA replication in bacteria

“…We were able to confirm over-replication of the termination area in a strain with a polA2 point mutation ( Midgley-Smith et al, 2018 ). These data are in line with the idea that the fork trap, together with specific proteins such as polymerase I, is involved in bringing DNA replication to a successful conclusion ( Markovitz, 2005 ; Duggin et al, 2008 ; Midgley-Smith et al, 2018 ; Rudolph et al, 2019 ). Similarly, absence of the terminator protein RTP in B. subtilis results in an increased formation of chromosomal dimers, which could arise from a related mechanism ( Lemon et al, 2001 ).…”

“…The specific termination site identified in the Gram-positive Bacillus subtilis ( Weiss et al, 1981 ) was later characterized to consist of a cluster of ter sites blocking progression of the clockwise replication fork complex, while a second cluster blocked progression of the counter-clockwise replication fork complex ( Wake, 1997 ; Neylon et al, 2005 ; Rudolph et al, 2019 ). While acting in a similar fashion, the ter sequences show very little similarity to the E. coli sequences.…”

“…PriA processing will result in the assembly of a new replication fork, the progression of which will not only result in chromosomal over-replication, but also the formation of a double-stranded DNA end ( Figure 5v ). dsDNA ends will be rapidly processed by the homologous recombination proteins RecBCD and RecA, leading to the formation of a displacement loop (D-loop) ( Rudolph et al, 2009 , 2013 , 2019 ; Dimude et al, 2016 ; Midgley-Smith et al, 2019 ). D-loops are yet another substrate for PriA, which means an opportunity for the formation of more replication forks, thus setting up a positive feedback loop of over-replication ( Figure 5vi ).…”

A Decade of Discovery—Eukaryotic Replisome Disassembly at Replication Termination

“…From this point onwards, progression is halted as the forks encounter the 'non-permissive' Tus-Ter complexes. It is here where the two forks thus converge and termination takes place (reviewed in [2,3]). It has been shown that without this tight control there is an accumulation of genomic instability and re-replication [4].…”

“…This is most likely caused by collisions between replication and transcription machineries, as the majority of bacterial genes are encoded on the leading strand and are thus transcribed co-directionally with replication (reviewed in [5]). The fact that multiple rounds of replication can take place at the same time on a bacterial chromosome, with new initiation events taking place before the previous round has completed [3], could also explain why terminating at a specific site is necessary. In bacteria, the sites of replication termination are, therefore, as well defined as the initiation sites.…”