Author:
Sanchez Aurore,Adam Céline,Rauh Felix,Duroc Yann,Ranjha Lepakshi,Lombard Bérangère,Mu Xiaojing,Loew Damarys,Keeney Scott,Cejka Petr,Guérois Raphaël,Klein Franz,Charbonnier Jean-Baptiste,Borde Valérie
Abstract
AbstractCrossovers generated during the repair of programmed double-strand breaks (DSBs) during homologous recombination are essential for fertility to allow accurate homolog segregation during the first meiotic division. Most crossovers arise through the cleavage of recombination intermediates by the Mlh1-Mlh3 (MutLγ) endonuclease and an elusive non-catalytic function of Exo1, and require the Polo kinase Cdc5. Here we show in budding yeast that MutLγ forms a constitutive complex with Exo1, and in meiotic cells transiently contacts the Msh4-Msh5 (MutSγ) heterodimer, also required for crossover formation. We further show that MutLγ-Exo1 associates with recombination intermediates once they are committed to the crossover repair pathway, and then Exo1 recruits Cdc5 through a direct interaction that is required for activating MutLγ and crossover formation. Exo1 therefore serves as a non-catalytic matchmaker between Cdc5 and MutLγ. We finally show that in vivo, MutLγ associates with the vast majority of DSB hotspots, but at a lower frequency near centromeres, consistent with a strategy to reduce at-risk crossover events in these regions. Our data highlight the tight temporal and spatial control of the activity of a constitutive, potentially harmful, nuclease.
Publisher
Cold Spring Harbor Laboratory
Cited by
3 articles.
订阅此论文施引文献
订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献