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The Srs2 helicase prevents recombination by disrupting Rad51 nucleoprotein filaments


Homologous recombination is a ubiquitous process with key functions in meiotic and vegetative cells for the repair of DNA breaks. It is initiated by the formation of single-stranded DNA on which recombination proteins bind to form a nucleoprotein filament that is active in searching for homology, in the formation of joint molecules and in the exchange of DNA strands1. This process contributes to genome stability but it is also potentially dangerous to cells if intermediates are formed that cannot be processed normally and thus are toxic or generate genomic rearrangements. Cells must therefore have developed strategies to survey recombination and to prevent the occurrence of such deleterious events. In Saccharomyces cerevisiae, genetic data have shown that the Srs2 helicase negatively modulates recombination2,3, and later experiments suggested that it reverses intermediate recombination structures4,5,6,7. Here we show that DNA strand exchange mediated in vitro by Rad51 is inhibited by Srs2, and that Srs2 disrupts Rad51 filaments formed on single-stranded DNA. These data provide an explanation for the anti-recombinogenic role of Srs2 in vivo and highlight a previously unknown mechanism for recombination control.

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Figure 1: Purification, ATPase and helicase activities of Srs2.
Figure 2: Srs2 inhibits DNA strand exchange catalysed by Rad51.
Figure 3: Disruption of Rad51 presynaptic filament by Srs2 as examined by electron microscopy.

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We thank L. Miccoli, D. Biard and J. Angulo for advice on recombinant baculovirus preparation and protein purification. P. Bertrand and C. Auvin for confirming the identity of Srs2 by MALDI–TOF mass spectrometry, and S. Gangloff, N. Kantake, L. Leloup, L. Maloisel, J. New and T. Robert for comments and discussions. This work was supported by the Commissariat à l'Energie Atomique, the Centre National de la Recherche Scientifique and Électricité de France.

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Correspondence to Xavier Veaute or Francis Fabre.

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Veaute, X., Jeusset, J., Soustelle, C. et al. The Srs2 helicase prevents recombination by disrupting Rad51 nucleoprotein filaments. Nature 423, 309–312 (2003).

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