TDM1 Regulation Determines the Number of Meiotic Divisions.

TDM1 Regulation Determines the Number of Meiotic Divisions.
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TDM1法规确定减数分裂分裂的数量。

DOI:
10.1371/journal.pgen.1005856
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发表时间:
2016-02
期刊:
影响因子:
4.5
通讯作者:
Mercier R
Mercier R
中科院分区:
生物学2区
文献类型:
--
作者:
Cifuentes M;Jolivet S;Cromer L;Harashima H;Bulankova P;Renne C;Crismani W;Nomura Y;Nakagami H;Sugimoto K;Schnittger A;Riha K;Mercier R

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细胞周期控制必须在减数分裂时进行修改,以允许两次分裂遵循单轮DNA复制,导致倍性降低。确保减数分裂在第二次分裂结束而不是在第一次分裂结束时终止的机制知之甚少。我们在这里表明,拟南芥TDM 1,这是以前已被证明是必不可少的减数分裂终止,直接与后期促进复合物。此外,TDM 1中保守的细胞周期蛋白依赖性激酶(CDK)磷酸化位点(T16-P17)的突变主要引起第一次分裂后减数分裂提前终止,以及二倍体孢子和配子的产生。CDKA;1-CYCA 1.2/TAM复合物是防止减数分裂提前退出所必需的,在体外T16磷酸化TDM 1。最后,虽然CYCA 1;2/TAM先前显示仅在减数分裂I中表达,但TDM 1在整个减数分裂中存在。这些数据,连同上位性分析,使我们提出,TDM 1是APC/C组件,其功能是确保减数分裂终止在减数分裂II结束时,其活性被抑制在减数分裂I的CDKA;1-TAM介导的磷酸化,以防止过早减数分裂退出。这提供了一种分子机制,用于分别在减数分裂I和II结束时进行额外一轮分裂或不进行额外一轮分裂的差异决定。减数分裂是有性生殖生物体的一个基本过程,它在种群内创造遗传多样性。减数分裂的一个关键特征是在受精前染色体数目从两组减少到一组。这种染色体数目的减少是由于单轮DNA复制后的两次细胞分裂。在这项研究中,我们分析了控制细胞分裂次数的机制,确保减数分裂终止发生在第二次减数分裂后,而不是在第一次分裂结束时。我们使用的模式植物拟南芥表明,基因TDM 1在调节减数分裂细胞分裂的核心作用。基因的完整性影响是否会发生一次、两次或三次减数分裂。我们进一步解释了TDM 1及其调节因子细胞周期蛋白TAM之间的关系,以及它们如何共同作用产生染色体数量减少的生殖细胞。这种严格控制的机制确保了正确数量的染色体从一代传递到下一代。
Cell cycle control must be modified at meiosis to allow two divisions to follow a single round of DNA replication, resulting in ploidy reduction. The mechanisms that ensure meiosis termination at the end of the second and not at the end of first division are poorly understood. We show here that Arabidopsis thaliana TDM1, which has been previously shown to be essential for meiotic termination, interacts directly with the Anaphase-Promoting Complex. Further, mutations in TDM1 in a conserved putative Cyclin-Dependant Kinase (CDK) phosphorylation site (T16-P17) dominantly provoked premature meiosis termination after the first division, and the production of diploid spores and gametes. The CDKA;1-CYCA1.2/TAM complex, which is required to prevent premature meiotic exit, phosphorylated TDM1 at T16 in vitro. Finally, while CYCA1;2/TAM was previously shown to be expressed only at meiosis I, TDM1 is present throughout meiosis. These data, together with epistasis analysis, lead us to propose that TDM1 is an APC/C component whose function is to ensure meiosis termination at the end of meiosis II, and whose activity is inhibited at meiosis I by CDKA;1-TAM-mediated phosphorylation to prevent premature meiotic exit. This provides a molecular mechanism for the differential decision of performing an additional round of division, or not, at the end of meiosis I and II, respectively. Meiosis is a fundamental process for sexually reproducing organisms that creates genetic diversity within populations. A key feature of meiosis is the reduction of the number of chromosomes, from two sets to one set, prior to fertilization. This reduction in chromosome number is due to two cell divisions following a single round of DNA replication. In this study, we analysed the mechanism which controls the number of cell divisions, ensuring that meiotic termination occurs after the second meiotic division, and not at the end of the first division. We used the model plant Arabidopsis thaliana to show that the gene TDM1 has a central role in regulating meiotic cell divisions. The integrity of the gene affects whether one, two or three meiotic divisions will occur. We further explain the relationship between TDM1 and its regulator the cyclin TAM, and how they work together to produce reproductive cells with a reduced number of chromosomes. This tightly controlled mechanism ensures the transmission of the correct number of chromosomes from one generation to the next.