A novel function for CDK2 activity at meiotic crossover sites.
A novel function for CDK2 activity at meiotic crossover sites.
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DOI：
10.1371/journal.pbio.3000903
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发表时间：
2020-10
期刊：
影响因子：
9.8
通讯作者：
Kaldis P
中科院分区：
文献类型：
--
作者：
Palmer N;Talib SZA;Singh P;Goh CMF;Liu K;Schimenti JC;Kaldis P
后代的遗传多样性是由减数分裂重组诱导的，减数分裂重组在源自减数分裂双链断裂（DSB）的>200个位点处的同源物之间启动。在该初始池中，每个同源物对仅1-2个DSB将被指定形成减数分裂交换（CO），其中在亲本染色体之间发生相互遗传交换。已知细胞周期蛋白依赖性激酶2（CDK 2）定位于标记初始CO位点的所谓“晚期重组结节”（LRN）。然而，CDK 2激酶活性在CO形成过程中的作用仍然不确定。在这里，我们描述了2 Cdk 2点突变体的活性升高或降低，分别表型。CDK 2活性升高与LRN相关蛋白的数量增加相关，包括CDK 2本身和MutLγ复合物的MutL同源物1（MLH 1）组分，但不会导致CO数量增加。相反，CDK 2活性降低导致在减数分裂前期I期间完全不存在CO形成。我们的数据表明，CDK 2在调节MLH 1焦点数量中起重要作用，并且该激酶的活性是减数分裂CO形成的关键调节因子。细胞周期蛋白依赖性激酶CDK 2对生育力至关重要，并调节减数分裂的几个阶段。这项研究表明，增加CDK 2活性导致减数分裂交叉的数量增加，而较低的CDK 2活性阻止交叉，这表明CDK 2在交叉形成中起着重要作用，是交叉指定过程的关键调节因子。
Genetic diversity in offspring is induced by meiotic recombination, which is initiated between homologs at >200 sites originating from meiotic double-strand breaks (DSBs). Of this initial pool, only 1–2 DSBs per homolog pair will be designated to form meiotic crossovers (COs), where reciprocal genetic exchange occurs between parental chromosomes. Cyclin-dependent kinase 2 (CDK2) is known to localize to so-called “late recombination nodules” (LRNs) marking incipient CO sites. However, the role of CDK2 kinase activity in the process of CO formation remains uncertain. Here, we describe the phenotype of 2 Cdk2 point mutants with elevated or decreased activity, respectively. Elevated CDK2 activity was associated with increased numbers of LRN-associated proteins, including CDK2 itself and the MutL homolog 1 (MLH1) component of the MutLγ complex, but did not lead to increased numbers of COs. In contrast, reduced CDK2 activity leads to the complete absence of CO formation during meiotic prophase I. Our data suggest an important role for CDK2 in regulating MLH1 focus numbers and that the activity of this kinase is a key regulatory factor in the formation of meiotic COs. The cyclin-dependent kinase CDK2 is essential for fertility and regulates several stages of meiosis. This study reveals that increased CDK2 activity leads to elevated numbers of meiotic crossovers, whereas lower CDK2 activity prevents crossovers, suggesting that CDK2 plays an important role in crossover formation and is a key regulator of the crossover designation process.
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影响因子：
11.8
作者：
Arter M;Hurtado-Nieves V;Oke A;Zhuge T;Wettstein R;Fung JC;Blanco MG;Matos J
通讯作者：
Matos J
DOI：
10.1042/bcj20160607
发表时间：
2016-09-15
期刊：
The Biochemical journal
影响因子：
--
作者：
Chauhan S;Diril MK;Lee JH;Bisteau X;Manoharan V;Adhikari D;Ratnacaram CK;Janela B;Noffke J;Ginhoux F;Coppola V;Liu K;Tessarollo L;Kaldis P
通讯作者：
Kaldis P
影响因子：
3.3
作者：
Falque, M.;Mercier, R.;Martin, O. C.
通讯作者：
Martin, O. C.
影响因子：
1.6
作者：
ASHLEY, T;PLUG, AW;WARD, DC
通讯作者：
WARD, DC
影响因子：
3.3
作者：
DESAI, D;GU, Y;MORGAN, DO
通讯作者：
MORGAN, DO