Avoiding chromosome pathology when replication forks collide

Chromosome duplication normally initiates via the assembly of replication fork complexes at defined origins(1,2). DNA synthesis by any one fork is thought to cease when it meets another travelling in the opposite direction, at which stage the replication machinery may simply dissociate before the nascent strands are finally ligated. But what actually happens is not clear. Here we present evidence consistent with the idea that every fork collision has the potential to threaten genomic integrity. In Escherichia coli this threat is kept at bay by RecG DNA translocase(3) and by single-strand DNA exonucleases. Without RecG, replication initiates where forks meet via a replisome assembly mechanism normally associated with fork repair, replication restart and recombination(4,5), establishing new forks with the potential to sustain cell growth and division without an active origin. This potential is realised when roadblocks to fork progression are reduced or eliminated. It relies on the chromosome being circular, reinforcing the idea that replication initiation is triggered repeatedly by fork collision. The results reported raise the question of whether replication fork collisions have pathogenic potential for organisms that exploit multiple origins to replicate each chromosome.