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

journal contribution
posted on 2023-06-07, 20:37 authored by Sarah Lambert, Ken'ichi Mizuno, Joël Blaisonneau, Sylvain Martineau, Roland Chanet, Karine Fréon, Jo Murray, Antony CarrAntony Carr, Giuseppe Baldacci
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.

History

Publication status

  • Published

Journal

Molecular Cell

ISSN

1097-2765

Issue

3

Volume

39

Page range

346-359

Pages

14.0

Department affiliated with

  • Sussex Centre for Genome Damage Stability Publications

Full text available

  • No

Peer reviewed?

  • Yes

Legacy Posted Date

2012-02-06

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