Journal Article

Mechanisms of DNA replication termination

Dewar, James M., Walter, Johannes C.

2017

Overview

Key Points Termination of DNA replication occurs when two replication forks meet on the same stretch of DNA, during which the following events occur, although not necessarily in this order: forks converge until all intervening DNA is unwound; any remaining gaps are filled and ligated; catenanes are removed; and replication proteins are unloaded. In eukaryotes, most termination sites are determined stochastically by the location of replication initiation sites. In bacteria, termination generally occurs at a specific locus. Replication termination can be a problematic process. Termination of simian virus 40 (SV40) replication involves the stalling of converging forks, and bacterial termination is prone to inducing re-replication. By contrast, fork stalling or re-replication have not been observed during unperturbed termination in eukaryotes. Topological stress accumulates between converging forks and is relieved by the generation of pre-catenanes, which are removed by type II topoisomerases. During bacterial and SV40 termination, type II topoisomerases are required for fork convergence, but in eukaryotes they are dispensable for this purpose. After forks converge, any remaining catenanes are removed by a type II topoisomerase. In eukaryotes, gaps are readily filled by the extension of the leading strands, but in bacteria and SV40 this process is less well-defined. In eukaryotes, a dedicated replisome removal pathway has recently been identified, which operates late during termination, after the DNA is fully replicated. It is unclear whether any comparable pathway exists in bacteria. The termination of DNA replication involves convergence of replication forks, the completion of DNA synthesis, replisome disassembly and the decatenation of daughter DNA molecules. Recent discoveries illustrate how replisome disassembly in eukaryotes is controlled by E3 ubiquitin ligases and how this activity is regulated to avoid genome instability. Genome duplication is carried out by pairs of replication forks that assemble at origins of replication and then move in opposite directions. DNA replication ends when converging replication forks meet. During this process, which is known as replication termination, DNA synthesis is completed, the replication machinery is disassembled and daughter molecules are resolved. In this Review, we outline the steps that are likely to be common to replication termination in most organisms, namely, fork convergence, synthesis completion, replisome disassembly and decatenation. We briefly review the mechanism of termination in the bacterium Escherichia coli and in simian virus 40 (SV40) and also focus on recent advances in eukaryotic replication termination. In particular, we discuss the recently discovered E3 ubiquitin ligases that control replisome disassembly in yeast and higher eukaryotes, and how their activity is regulated to avoid genome instability.

• Publisher: Nature Publishing Group UK,Nature Publishing Group
• Subject: 631/337/151 / 631/337/151/2353 / Biochemistry / Cancer Research / Cell Biology / Chemical synthesis / Convergence / Deoxyribonucleic acid / Developmental Biology / Dismantling / DNA / DNA - genetics / DNA biosynthesis / DNA replication / DNA Replication - genetics / DNA Replication - physiology / E coli / Escherichia coli - genetics / Eukaryotes / Genomes / Genomic instability / Genomic Instability - genetics / Genomic Instability - physiology / Health aspects / Life Sciences / Replication / Replication fork / Replication forks / Replication origins / review-article / Saccharomyces cerevisiae - genetics / Stability / Stem Cells / Ubiquitin / Ubiquitin-protein ligase / Viruses / Yeast