“Restarting” Replication Forks That Never Stopped

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The misleading terms “induced replisome reactivation”, “blocked replisome” and “replication restart” were introduced in the late1980’s to describe the immediate inhibition and subsequent robust resumption of DNA synthesis in UV-irradiated /E. coli/.  These authors failed to appreciate that the replication fork passes multiple UV lesions in both strands before the robust resumption of synthesis occurs.  In fact, their data, in contrast to their interpretation, is completely consistent with our early studies in excision defective /E. coli/ in which it was demonstrated that after UV, although DNA synthesis was inhibited, replication proceeded past many template strand lesions to generate short pieces that were later transformed into normal size DNA, often involving strand exchanges.
In the early 1990’s we proposed a model in which the helicase and the polymerase at the replication fork become uncoupled when the DnaB helicase proceeds past leading strand lesions while the Pol III holoenzyme stalls at
the lesion to generate a single-strand region extending between the helicase and the polymerase.  A subsequent priming event can then occur on this newly-generated single-stranded segment to restart the leading strand.  We
also suggested that the most likely way for this to happen is “a DnaB-DnaG priming event at the fork that is analogous to the priming of the lagging-strand fragments”.
The transient inhibition of DNA synthesis after UV occurs because the replicative helicase slows to about 50 bp/s whenever it becomes uncoupled from a replicative polymerase blocked at a template strand lesion.  These
predictions have now been supported by data from several laboratories.
Rupp, W. D. 1996. DNA Repair Mechanisms, p. 2277-2294. /In/ F. Neidhardt /et al/ (ed.), /Escherichia coli/ and /Salmonella/, 2nd ed., vol. 2. ASM,
Washington, DC.