Replisome assembly and the direct restart of stalled replication forks

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Abstract
Replication forks can stall because of an encounter with a DNA-template lesion. The template damage can be from either exogenous or endogenous sources. Stalled forks can lead to genomic instability. To suppress this potential instability, the bacterial cell uses specialized replication-restart pathways that enable fork reactivation outside of the origin of replication. In general, restart involves three steps: processing of the stalled fork to generate proper strand configurations; structure-specific recognition of the stalled fork by one of the restart pathways and assembly of a replisome; and removal of the blocking DNA lesion. Recent findings have shown that the restart systems can prime synthesis of both the nascent leading and lagging strands. This unexpected property indicates that replication can resume downstream of the blocking DNA lesion prior to its removal, presumably leaving a gap behind that would be filled by homologous recombination. Although no obvious homologues of replication-restart components have been identified in eukaryotes, gaps in nascent DNA have been detected in various higher organisms, implying similar and universal fork repair mechanisms between species.