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Τρίτη 19 Ιουνίου 2018

Regulated Crossing-Over Requires Inactivation of Yen1/GEN1 Resolvase during Meiotic Prophase I

Publication date: 18 June 2018
Source:Developmental Cell, Volume 45, Issue 6
Author(s): Meret Arter, Vanesa Hurtado-Nieves, Ashwini Oke, Tangna Zhuge, Rahel Wettstein, Jennifer C. Fung, Miguel G. Blanco, Joao Matos
During meiosis, crossover recombination promotes the establishment of physical connections between homologous chromosomes, enabling their bipolar segregation. To ensure that persistent recombination intermediates are disengaged prior to the completion of meiosis, the Yen1(GEN1) resolvase is strictly activated at the onset of anaphase II. Whether controlled activation of Yen1 is important for meiotic crossing-over is unknown. Here, we show that CDK-mediated phosphorylation of Yen1 averts its pervasive recruitment to recombination intermediates during prophase I. Yen1 mutants that are refractory to phosphorylation resolve DNA joint molecules prematurely and form crossovers independently of MutLγ, the central crossover resolvase during meiosis. Despite bypassing the requirement for MutLγ in joint molecule processing and promoting crossover-specific resolution, unrestrained Yen1 impairs the spatial distribution of crossover events, genome-wide. Thus, active suppression of Yen1 function, and by inference also of Mus81-Mms4(EME1) and Slx1-Slx4(BTBD12) resolvases, avoids precocious resolution of recombination intermediates to enable meiotic crossover patterning.

Graphical abstract

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Teaser

In many organisms, the faithful disjunction of maternal and paternal centromeres during meiosis I requires homologous recombination and crossing-over. Here, Arter et al. show that phosphorylation-mediated inactivation of the Yen1/GEN1 resolvase, during prophase I, avoids the precocious resolution of recombination intermediates to enable controlled crossover formation throughout the genome.


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