Regulated Crossing-Over Requires Inactivation of Yen1/GEN1 Resolvase during Meiotic Prophase I.
Regulated Crossing-Over Requires Inactivation of Yen1/GEN1 Resolvase during Meiotic Prophase I.
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DOI：
10.1016/j.devcel.2018.05.020
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发表时间：
2018-06-18
影响因子：
11.8
通讯作者：
Matos J
中科院分区：
文献类型：
--
作者：
Arter M;Hurtado-Nieves V;Oke A;Zhuge T;Wettstein R;Fung JC;Blanco MG;Matos J
在减数分裂过程中，交叉重组促进同源染色体之间物理连接的建立，使它们能够进行双极分离。为了确保持续的重组中间体在减数分裂完成之前脱离，Yen 1（GEN 1）解离酶在后期II开始时被严格激活。控制激活Yen 1是否对减数分裂交换很重要尚不清楚。在这里，我们表明，CDK介导的磷酸化Yen 1避免其广泛的招聘重组中间体在前期I。Yen 1突变体对磷酸化不敏感，过早地分解DNA连接分子，并独立于MutLγ（减数分裂期间的中心交换分解酶）形成交换。尽管在联合分子加工中绕过了MutLγ的要求并促进了交叉特异性分辨率，但不受限制的Yen 1损害了全基因组交叉事件的空间分布。因此，Yen 1功能的主动抑制-以及通过推断Mus 81-Mms 4（EME 1）和Slx 1-Slx 4（BTBD 12）解离酶的主动抑制-避免了重组中间体的早熟解离，从而使减数分裂交叉模式化成为可能。在许多生物中，在减数分裂I期间，母本和父本着丝粒的忠实分离需要同源重组和交换。在此，Arter等人表明，在前期I期间，磷酸化介导的Yen 1/GEN 1解离酶的失活避免了重组中间体的过早分解，从而能够在整个基因组中形成受控的交换。
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. 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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