Replication fork barriers: pausing for a break or stalling for time?

Karim Labib, Ben Hodgson

    Research output: Contribution to journalReview articlepeer-review

    101 Citations (Scopus)

    Abstract

    Defects in chromosome replication can lead to translocations that are thought to result from recombination events at stalled DNA replication forks. The progression of forks is controlled by an essential DNA helicase, which unwinds the parental duplex and can stall on encountering tight protein-DNA complexes. Such pause sites are hotspots for recombination and it has been proposed that stalled replisomes disassemble, leading to fork collapse. However, in both prokaryotes and eukaryotes it now seems that paused forks are surprisingly stable, so that DNA synthesis can resume without recombination if the barrier protein is removed. Recombination at stalled forks might require other events that occur after pausing, or might be dependent on features of the surrounding DNA sequence. These findings have important implications for our understanding of the regulation of genome stability in eukaryotic cells, in which pausing of forks is mediated by specific proteins that are associated with the replicative helicase.

    Original languageEnglish
    Pages (from-to)346-353
    Number of pages8
    JournalEMBO Reports
    Volume8
    Issue number4
    DOIs
    Publication statusPublished - Apr 2007

    Keywords

    • SCHIZOSACCHAROMYCES-POMBE
    • recombination
    • ESCHERICHIA-COLI CHROMOSOME
    • checkpoint
    • RIBOSOMAL DNA
    • BLOCK PROTEIN FOB1
    • DAMAGE RESPONSE
    • FISSION YEAST
    • DNA replication fork barriers
    • replisome
    • RNA-POLYMERASE-I
    • mini-chromosome maintenance helicase
    • MITOTIC RECOMBINATION
    • EUKARYOTIC DNA-REPLICATION
    • SACCHAROMYCES-CEREVISIAE

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