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

Lambert, Sarah, Mizuno, Ken'ichi, Blaisonneau, Joël, Martineau, Sylvain, Chanet, Roland, Fréon, Karine, Murray, Johanne M, Carr, Antony M and Baldacci, Giuseppe (2010) Homologous recombination restarts blocked replication forks at the expense of genome rearrangements by template exchange. Molecular Cell, 39 (3). pp. 346-359. ISSN 1097-2765

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Abstract

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.

Item Type: Article
Schools and Departments: School of Life Sciences > Sussex Centre for Genome Damage and Stability
Depositing User: Ken'ichi Mizuno
Date Deposited: 06 Feb 2012 18:35
Last Modified: 10 Jul 2013 10:01
URI: http://sro.sussex.ac.uk/id/eprint/17266
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