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调控同源重组需要 Yen1/GEN1 核酸内切酶在减数分裂前期 I 失活。

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

机构信息

Institute of Biochemistry, HPM D6.5 - ETH Zürich, Otto-Stern-Weg 3, 8093 Zürich, Switzerland.

Departamento de Bioquímica e Bioloxía Molecular, CIMUS, Universidade de Santiago de Compostela - IDIS, 15706 Santiago de Compostela, Spain.

出版信息

Dev Cell. 2018 Jun 18;45(6):785-800.e6. doi: 10.1016/j.devcel.2018.05.020.

Abstract

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.

摘要

在减数分裂过程中,交叉重组促进同源染色体之间建立物理连接,使其能够进行两极分离。为了确保在减数分裂完成之前,持久的重组中间体能够脱离,Yen1(GEN1)解旋酶在后期 II 开始时被严格激活。然而,Yen1 的受控激活对于减数分裂交叉是否重要尚不清楚。在这里,我们表明 CDK 介导的 Yen1 磷酸化避免了其在前期 I 期间对重组中间体的普遍募集。对磷酸化有抗性的 Yen1 突变体过早地解决 DNA 连接分子,并独立于 MutLγ(减数分裂中中心的交叉解旋酶)形成交叉。尽管绕过了 MutLγ 在连接分子处理中的要求,并促进了交叉特异性的解决,但不受控制的 Yen1 损害了交叉事件的空间分布,在全基因组范围内。因此,积极抑制 Yen1 功能,以及推理的 Mus81-Mms4(EME1)和 Slx1-Slx4(BTBD12)解旋酶功能,避免了重组中间体的过早解决,从而实现了减数分裂交叉模式。

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