Replication fork convergence at termination: A multistep process

Abstract

Termination of replication occurs when two forks converge, an important but understudied process. In PNAS, a report from the Courcelle group examines replication termination using deep-sequencing genomic profiling of replicating cells to obtain copy number information about head-on collision of replication forks in different genetic backgrounds (1). Mutations in the SbcC-SbcD (SbcCD) and ExoI nucleases of Escherichia coli result in overreplication of DNA at the terminal replication zone where forks converge, implying that extra DNA is made upon termination and these nucleases are needed to excise the extra DNA. Furthermore, mutational studies of the RecBCD helicase/nuclease reveal that it acts at a step after SbcCD/Exo1 action to complete the processing of overreplicated DNA generated by fork convergence. Overreplication upon termination in E. coli has been reported earlier, but the DNA structures produced, and subsequent processing steps are not well understood (2⇓–4). The report by Wendel et al. (1) demonstrates that termination of replication is a complex process orchestrated by many factors, and implies specific roles of the enzymes involved. Termination of replication, when two replication forks meet head-on, has the potential for deleterious consequences. For example, amplifications, resections leading to deletions, and other DNA rearrangements are associated with defective replication termination (1⇓⇓–4). Extensive studies have outlined the events that activate origins and advance replication forks in bacteria and eukaryotes (5, 6), but little is known about the replication termination process, possibly because termination does not occur at a defined sequence, making it difficult to study. The circular chromosome of E. coli has been an attractive model to study the termination process for two main reasons. First, E. coli has only one origin ( oriC ) that forms bidirectional forks that meet head-on roughly half way around the circular genome from the origin. Second, E. … [↵][1]1To whom correspondence should be addressed. Email: odonnel{at}rockefeller.edu. [1]: #xref-corresp-1-1