Avoiding chromosome pathology when replication forks collide

Nature. 2013 Aug 29;500(7464):608-11. doi: 10.1038/nature12312. Epub 2013 Jul 28.

Abstract

Chromosome duplication normally initiates through the assembly of replication fork complexes at defined origins. 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 and by single-strand DNA exonucleases. Without RecG, replication initiates where forks meet through a replisome assembly mechanism normally associated with fork repair, replication restart and recombination, establishing new forks with the potential to sustain cell growth and division without an active origin. This potential is realized 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 several origins to replicate each chromosome.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Bacterial Proteins / metabolism
  • Bacteriophages / genetics
  • Bacteriophages / physiology
  • Chromosomes, Bacterial / genetics
  • Chromosomes, Bacterial / metabolism*
  • DNA Helicases / metabolism
  • DNA Replication*
  • DNA, Bacterial
  • DNA, Circular
  • DNA, Single-Stranded
  • DNA-Binding Proteins / metabolism
  • Escherichia coli / enzymology
  • Escherichia coli / genetics*
  • Escherichia coli / growth & development
  • Escherichia coli / virology
  • Escherichia coli Proteins / metabolism
  • Exodeoxyribonuclease V / metabolism
  • Exonucleases / metabolism
  • Genetic Markers / genetics
  • Genomic Instability
  • Replication Origin*

Substances

  • Bacterial Proteins
  • DNA, Bacterial
  • DNA, Circular
  • DNA, Single-Stranded
  • DNA-Binding Proteins
  • DnaA protein, Bacteria
  • Escherichia coli Proteins
  • Genetic Markers
  • RecG protein, E coli
  • Exonucleases
  • Exodeoxyribonuclease V
  • priA protein, E coli
  • DNA Helicases

Associated data

  • GEO/GSE41975