Gross chromosomal rearrangements and elevated recombination at an inducible site-specific replication fork barrier.
Genomic rearrangements linked to aberrant recombination are associated with cancer and human genetic diseases. Such recombination has indirectly been linked to replication fork stalling. Using fission yeast, we have developed a genetic system to block replication forks at nonhistone/DNA complexes located at a specific euchromatic site. We demonstrate that stalled replication forks lead to elevated intrachromosomal and ectopic recombination promoting site-specific gross chromosomal rearrangements. We show that recombination is required to promote cell viability when forks are stalled, that recombination proteins associate with sites of fork stalling, and that recombination participates in deleterious site-specific chromosomal rearrangements. Thus, recombination is a "double-edged sword," preventing cell death when the replisome disassembles at the expense of genetic stability.
Lambert
Sarah
S
Genome Damage and Stability Centre, University of Sussex, Brighton BN1 9RQ, UK.
Watson
Adam
A
Sheedy
Daniel M
DM
Martin
Ben
B
Carr
Antony M
AM
D002875:Chromosomes / Q000502:physiology*; D004261:DNA Replication / Q000502:physiology*; D004268:DNA-Binding Proteins / Q000378:metabolism; D019084:Fluorescent Antibody Technique, Indirect; D011995:Recombination, Genetic / Q000502:physiology*; D012568:Schizosaccharomyces / Q000235:genetics / Q000502:physiology; D029702:Schizosaccharomyces pombe Proteins / Q000378:metabolism
D004268:DNA-Binding Proteins; D029702:Schizosaccharomyces pombe Proteins; C085412:rad52 protein, S pombe