Molecular requirements for nuclear envelope attachment and movements of meiotic telomeres

在减数分裂的第一次分裂过程中，母本和父本染色体的准确分离需要同源染色体之间的配对、突触和重组。在准备用于分离的同源物时，一个非常核心的方面是端粒的定向运动，最终形成花束，这反过来对忠实的同源基因分类至关重要，因此对基因组单倍化是必不可少的。这种端粒驱动的染色体收集是一种普遍的现象，几乎适用于每一种有性繁殖的真核生物。然而，到目前为止，端粒与核膜连接所需的分子机制及其定向运动还知之甚少。为了了解这一极其重要的问题，我们在过去的一段时间里一直致力于这些过程中涉及的蛋白质成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，我们可以对我们目前关于端粒如何附着到核膜上的知识做出重大贡献。我们目前的兴趣在于阐明核膜及其成分(特别是减数分裂层蛋白C2、太阳域蛋白以及未知的结合伙伴)在端粒附着和运动中的作用。我们将采取各种不同的方法，包括对我们最近产生的Lamin C2‘基因敲除’小鼠的详细分析，以及关于对减数分裂端粒行为的潜在影响的进一步基因敲除模型的分析。此外，我们还将寻找端粒附着和/或运动所需的未知蛋白质。最近，我们分离了两个有希望的候选人，现在应该详细说明这两个候选人的特征。

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.