Molecular requirements for nuclear envelope attachment and movements of meiotic telomeres

在减数分裂的第一次分裂期间，母本和父本染色体的精确分离需要同源物之间的配对、联会和重组。制备用于分离的同源物的一个非常核心的方面是端粒的定向运动，其在花束形成中达到高潮，这反过来对于忠实的同源物分类至关重要，因此对于基因组单倍体化至关重要。这种端粒驱动的染色体聚集是一种普遍现象，几乎适用于每一种有性繁殖的真核生物。然而，到目前为止，端粒附着到核膜所需的分子机制及其定向运动知之甚少。为了了解这个至关重要的问题，我们在过去的一段时间里一直致力于这些过程中所涉及的蛋白质组分的鉴定以及分子和功能表征。在拟议的项目中，我们希望跟进我们最近成功的调查，通过这些调查，我们可以在端粒如何附着在核膜上方面为我们目前的知识做出重大贡献。我们目前的兴趣在于阐明的作用，核膜及其组件（特别是减数分裂核纤层蛋白C2，太阳结构域蛋白，以及尚未未知的结合伙伴）在端粒的附着和运动。我们将进行各种不同的方法，包括我们最近产生的核纤层蛋白C2 '敲除'小鼠的详细分析，以及进一步敲除模型的分析，对减数分裂端粒行为的潜在影响。此外，我们将寻找端粒附着和/或运动所需的未知蛋白质。最近，我们已经分离出两个有希望的候选人，现在应该详细描述。

Accurate separation of maternal and paternal chromosomes during the first division of meiosis requires pairing, synapsis and recombination between the homologs. A very central aspect in preparing homologs for separation is the directed movement of telomeres that culminates in bouquet-formation, which in turn is crucial for faithful homolog assortment and hence essential for genome haploidization. This kind of telomere driven chromosome gathering is a widespread phenomenon that applies for almost every sexually reproducing eukaryote. However, up to the present the molecular mechanisms required for telomere attachment to the nuclear envelope and their directed movements are poorly understood. To learn about this vitally important issue we for some time past are engaged with the identification as well as molecular and functional characterization of protein components involved in these processes. Within the proposed project we would like to follow up our recent successful investigations by which we could significantly contribute to our current knowledge in terms of how telomeres attach to the nuclear envelope. Our current interest lies in elucidating the role of the nuclear envelope and its components (particularly of meiotic lamin C2, SUN-domain proteins, as well as yet unknown binding partners) in telomere attachment and movements. We will carry out a variety of different approaches, including the detailed analysis of our recently generated lamin C2 ‘knockout’ mouse as well as the analysis of further knockout models with respect to potential effects on meiotic telomere behaviour. Furthermore, we will hunt for yet unknown proteins required for telomere attachment and/or movement. Recently, we have isolated two promising candidates that now should be characterized in detail.