Replication fork reactivation downstream of a blocked nascent leading strand

Nature. 2006 Feb 2;439(7076):557-62. doi: 10.1038/nature04329.


Unrepaired lesions in the DNA template pose a threat to accurate replication. Several pathways exist in Escherichia coli to reactivate a blocked replication fork. The process of recombination-dependent restart of broken forks is well understood, but the consequence of replication through strand-specific lesions is less well known. Here we show that replication can be restarted and leading-strand synthesis re-initiated downstream of an unrepaired block to leading-strand progression, even when the 3'-OH of the nascent leading strand is unavailable. We demonstrate that the loading by a replication restart system of a single hexamer of the replication fork helicase, DnaB, on the lagging-strand template is sufficient to coordinate priming by the DnaG primase of both the leading and lagging strands. These observations provide a mechanism for damage bypass during fork reactivation, demonstrate how daughter-strand gaps are generated opposite leading-strand lesions during the replication of ultraviolet-light-irradiated DNA, and help to explain the remarkable speed at which even a heavily damaged DNA template is replicated.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adenosine Triphosphatases / metabolism
  • Bacterial Proteins / metabolism
  • Biotin / metabolism
  • DNA / biosynthesis*
  • DNA / metabolism
  • DNA Helicases / metabolism
  • DNA Primase / metabolism
  • DNA Repair
  • DNA Replication / physiology*
  • DnaB Helicases
  • Endodeoxyribonucleases / metabolism
  • Escherichia coli / enzymology
  • Escherichia coli / genetics*
  • Escherichia coli Proteins / metabolism
  • Exodeoxyribonucleases / metabolism
  • Models, Genetic
  • Templates, Genetic


  • Bacterial Proteins
  • Escherichia coli Proteins
  • PriC protein, E coli
  • Biotin
  • DNA
  • DNA Primase
  • Endodeoxyribonucleases
  • Exodeoxyribonucleases
  • dnaG protein, E coli
  • Adenosine Triphosphatases
  • dnaB protein, E coli
  • DNA Helicases
  • DnaB Helicases