Homologous recombination restarts blocked replication forks at the expense of genome rearrangements by template exchange

Template switching induced by stalled replication forks has recently been proposed to underlie complex genomic rearrangements. However, the resulting models are not supported by robust physical evidence. Here, we analyzed replication and recombination intermediates in a well-defined fission yeast sy...

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Veröffentlicht in:Molecular cell Jg. 39; H. 3; S. 346
Hauptverfasser: Lambert, Sarah, Mizuno, Ken'ichi, Blaisonneau, Joël, Martineau, Sylvain, Chanet, Roland, Fréon, Karine, Murray, Johanne M, Carr, Antony M, Baldacci, Giuseppe
Format: Journal Article
Sprache:Englisch
Veröffentlicht: United States 13.08.2010
Schlagworte:
DNA Helicases - genetics
DNA Helicases - metabolism
DNA Replication - physiology
DNA, Fungal - biosynthesis
DNA, Fungal - genetics
Genome, Fungal - physiology
Rad51 Recombinase - genetics
Rad51 Recombinase - metabolism
Rad52 DNA Repair and Recombination Protein - genetics
Rad52 DNA Repair and Recombination Protein - metabolism
Recombination, Genetic - physiology
Saccharomyces cerevisiae Proteins - genetics
Saccharomyces cerevisiae Proteins - metabolism
Schizosaccharomyces - genetics
Schizosaccharomyces - metabolism
Schizosaccharomyces pombe Proteins - genetics
Schizosaccharomyces pombe Proteins - metabolism
ISSN:1097-4164, 1097-4164
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Zusammenfassung:Template switching induced by stalled replication forks has recently been proposed to underlie complex genomic rearrangements. However, the resulting models are not supported by robust physical evidence. Here, we analyzed replication and recombination intermediates in a well-defined fission yeast system that blocks replication forks. We show that, in response to fork arrest, chromosomal rearrangements result from Rad52-dependent nascent strand template exchange occurring during fork restart. This template exchange occurs by both Rad51-dependent and -independent mechanisms. We demonstrate that Rqh1, the BLM homolog, limits Rad51-dependent template exchange without affecting fork restart. In contrast, we report that the Srs2 helicase promotes both fork restart and template exchange. Our data demonstrate that template exchange occurs during recombination-dependent fork restart at the expense of genome rearrangements.
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ISSN:1097-4164
1097-4164
DOI:10.1016/j.molcel.2010.07.015