Polo is not solo in meiosis
Polo is not solo in meiosis
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波罗在减数分裂中并不是单独的
DOI：
10.1080/15384101.2017.1411435
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发表时间：
2018
期刊：
影响因子：
4.3
通讯作者：
Tsubouchi Hideo
中科院分区：
文献类型：
--
作者：
Argunhan Bilge;Tsubouchi Tomomi;Tsubouchi Hideo
减数分裂是一种特殊的细胞分裂，它将生殖细胞的染色体数目减少一半，从而确保配子具有体细胞染色体的一半。这种倍性的降低是通过将单轮DNA复制与两次串联的核分裂（减数分裂I和减数分裂II）偶联来实现的。在减数分裂I中，同源体（即不同亲本来源的染色体）分离，而在减数分裂II中，姐妹染色单体分离。由于姐妹染色单体的分离也发生在有丝分裂中，正是同源体的分离使得减数分裂是独特的。具有讽刺意味的是，同源物的正确分离始于它们的配对。在早期前期I，称为联会复合体（SC）的蛋白质大分子开始形成。SC通过使同源物沿其整个长度沿着而促进同源物的配对，导致同源物之间重组中间体的形成。当细胞退出前期I时，SC突然解体，重组中间体转化为交叉。虽然SC对于有效的交换是必不可少的，但如果保持完整直到后期I，它将对抗负责分离同源物的微管力，可能导致严重的染色体不分离。尽管如此，与SC形成相反，对SC分解知之甚少[1]。芽殖酵母中从前期I退出是通过上调减数分裂的主要转录因子Ndt 80来实现的。在Ndt 80上调的数百个基因中，SC破坏所必需的唯一基因产物是Polo样激酶（波罗）[2]。我们最近报道，除了波罗，Dbf 4依赖性Cdc 7激酶（DDK）和细胞周期蛋白依赖性激酶（CDK）在调节SC分解中起重要作用[3]。SC拆卸的效率，通过免疫荧光显微镜测定，发现DDK-Polo相互作用强度表现出很强的正相关性。全细胞提取物的检查显示，SC解体与主要SC组分水平的急剧下降相关，表明DDK和波罗介导的解体机制涉及蛋白质破坏。此外，当Dbf 4或Cdc 7（分别包含DDK的调节和催化亚基）耗尽时，Polo驱动的SC破坏变得无效。同样，CDK的失活极大地阻碍了SC的破坏。然而，在这两种情况下，SC破坏仍然发生，尽管效率低下。这些发现强调了三种基本细胞周期激酶在促进SC破坏中的协调努力。而DDK活性在前期I较高，波罗水平相对较低，直到退出前期I。同时，CDK活性也通过细胞周期蛋白的上调而增强。因此，这三种激酶在减数分裂期间具有不同的活性谱。然而，DDK活性在中期I完成时通过后期促进复合物/环体介导的Dbf 4破坏而迅速消除，当所有三种激酶的活性一致时，有效地在细胞周期中产生狭窄的时间窗（图1）。在此时间范围内，三种激酶协同破坏SC。在分子水平上，波罗和CDK协同磷酸化前期I-中期I转换的Dbf 4;这种磷酸化对于有效的SC破坏很重要[4]。因此，Dbf 4充当涉及DDK、波罗和CDK的基于磷酸化的信号传导网络的枢纽。这种磷酸化然后触发下游级联反应以促进Polo介导的SC破坏。这可能涉及直接磷酸化的波罗通过.
Meiosis is a specialized cell division that reduces the chromosome number of germ cells by exactly half, thereby ensuring that gametes have precisely half the complement of chromosomes as somatic cells. This reduction in ploidy is achieved through the coupling of a single round of DNA replication with two tandem nuclear divisions, meiosis I and meiosis II. During meiosis I, homologs (ie, chromosomes of different parental origin) are separated, whereas in meiosis II, sister chromatids are separated. Since the separation of sister chromatids also occurs in mitosis, it is the separation of homologs that makes meiosis unique. Ironically, the correct separation of homologs starts with their pairing. In early prophase I, a proteinaceous macromolecule known as the synaptonemal complex (SC) begins to form. The SC facilitates the pairing of homologs by adhering them along their entire lengths, leading to the formation of recombination intermediates between homologs. As cells exit prophase I, the SC abruptly disassembles and the recombination intermediates are converted into crossovers. Although the SC is essential for efficient crossing over, if left intact until anaphase I, it would oppose the microtubule forces responsible for separating homologs, potentially resulting in severe chromosomal nondisjunction. Despite this, and in contrast to SC formation, relatively little is known about SC disassembly [1]. Exit from prophase I in budding yeast is achieved through upregulation of Ndt80, the master transcription factor of meiosis. From the hundreds of genes that Ndt80 upregulates, the only gene product essential for SC destruction is Polo-like kinase (Polo)[2]. We recently reported that, in addition to Polo, Dbf4-dependent Cdc7 kinase (DDK) and cyclin-dependent kinase (CDK) play important roles in regulating SC disassembly [3]. The efficiency of SC disassembly, as determined by immunofluorescence microscopy, was found to show a strong positive correlation with DDK-Polo interaction strength. Examination of whole cell extracts revealed that SC disassembly correlated with a drastic decline in the levels of major SC components, indicating that the disassembly mechanism mediated by DDK and Polo involves protein destruction. Moreover, upon depletion of Dbf4 or Cdc7, which comprise the regulatory and catalytic subunits of DDK, respectively, Polo-driven SC destruction became inefficient. Similarly, inactivation of CDK greatly hindered SC destruction. However, in both cases, SC destruction still occurred, albeit inefficiently. These findings highlighted a coordinated effort by three fundamental cell cycle kinases in promoting SC destruction. Whereas DDK activity is high in prophase I, Polo levels are relatively low until exit from prophase I. In parallel, CDK activity is also enhanced through the upregulation of cyclins. Thus, the three kinases have distinct activity profiles during meiosis. However, DDK activity is swiftly ablated at the completion of metaphase I through anaphase-promoting complex/cyclosomemediated destruction of Dbf4, effectively creating a narrow window of time in the cell cycle when the activities of all three kinases coincide (Fig. 1). It is within this timeframe that the three kinases collaborate to destroy the SC. At the molecular level, Polo and CDK collaboratively phosphorylate Dbf4 at the prophase I-metaphase I transition; this phosphorylation is important for efficient SC destruction [4]. Thus, Dbf4 serves as the hub of a phosphorylation-based signalling network involving DDK, Polo, and CDK. This phosphorylation then triggers a downstream cascade to promote Polo-mediated SC destruction. This could potentially involve direct phosphorylation of Polo by …
影响因子：
10.5
作者：
Sourirajan, Anuradha;Lichten, Michael
通讯作者：
Lichten, Michael