Replication fork reactivation downstream of a blocked nascent leading strand Journal Article

Authors: Heller, R. C.; Marians, K. J.
Article Title: Replication fork reactivation downstream of a blocked nascent leading strand
Abstract: 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. © 2006 Nature Publishing Group.
Keywords: nonhuman; dna replication; ultraviolet radiation; dna damage; dna repair; bacterial proteins; dna; escherichia coli; irradiation; models, genetic; dna flanking region; helicase; adenosine triphosphatases; enzymes; synthesis; dna helicases; synthesis (chemical); dna sequences; escherichia coli proteins; biotin; endodeoxyribonucleases; exodeoxyribonucleases; replication; dna template; reactivation; dna strand; dna strands; templates, genetic; dna b; dna primase; leading-strand progressions; dnab helicases
Journal Title: Nature
Volume: 439
Issue: 7076
ISSN: 0028-0836
Publisher: Nature Publishing Group  
Date Published: 2006-02-02
Start Page: 557
End Page: 562
Language: English
DOI: 10.1038/nature04329
PUBMED: 16452972
PROVIDER: scopus
Notes: --- - "Cited By (since 1996): 134" - "Export Date: 4 June 2012" - "CODEN: NATUA" - "Source: Scopus"
Citation Impact
MSK Authors
  1. Kenneth Marians
    129 Marians