Meiotic Chromosome Inheritance in Caenorhabditis

计划摘要 我们的研究旨在了解信徒背后的分子和细胞机制。 真核细胞染色体的遗传。我们的主要焦点是阐明秩序所需的事件 减数分裂中同源染色体的分离，这是二倍体生殖细胞的关键过程 产生单倍体配子。这些事件对有性繁殖生物体至关重要，因为 未能正确地执行它们会导致染色体非整倍体，这是流产的主要原因之一 人类的先天缺陷。在减数分裂前期，染色体经历了戏剧性和动态的程序 进行结构重组，为减数分裂做准备。此外，染色体遗传过程中 减数分裂依赖于双链DNA断裂(DSB)的形成和这些DSB的子集的修复 同源间交叉(CoS)。因为作为减数分裂重组启动事件的双链断裂 对基因组完整性构成威胁，减数分裂过程中基因组遗传的成功需要细胞保持 在COS的有益影响和由此产生的过程的潜在有害后果之间取得平衡 它们是生成的。我们研究的一个主要目标是了解减数分裂过程中的运作机制。 来实现这一关键的平衡。一个相互关联的目标是了解减数分裂特定的染色体是如何 建立、维护和重塑组织，以实现成功的同源分离 染色体。我们正在使用线虫，一种简单的后生生物来解决这些问题 尤其适用于强大的细胞学、遗传学、基因组学和 生物化学方法，其中所研究的事件特别容易获得。我们的目标是 MIRA计划是追求对减数分裂的系统水平的理解，基于对多个 减数分裂程序的不同方面是紧密相连的，系统的稳健性是一种 这种互联性的突现特性。我们的方法将建立在最近的技术进步和新的 在成熟的线虫实验系统中的发现，以及提供的机会 通过一个新引入的线虫种间杂交模型，对减数分裂程序在多个 级别。计划的调查领域将包括：阐明确保可靠地形成CO- 基于所有染色体对的连接；探索不同的事件和发育转变如何 减数分裂程序在时间和空间上是协调的；调查 减数分裂特有的染色体结构，促进和调节减数分裂重组，并使 染色体来感知和响应发生在远处的事件；寻求一种新的方法，旨在 理解同源词识别的基本基础。

Program Summary Our research is aimed at understanding the molecular and cellular mechanisms underlying the faithful inheritance eukaryotic chromosomes. Our primary focus is on elucidating the events required for the orderly segregation of homologous chromosomes during meiosis, the crucial process by which diploid germ cells generate haploid gametes. These events are of central importance to sexually reproducing organisms, since failure to execute them correctly leads to chromosomal aneuploidy, one of the leading causes of miscarriages and birth defects in humans. During meiotic prophase, chromosomes undergo a dramatic and dynamic program of structural reorganization in preparation for the meiotic divisions. Moreover, chromosome inheritance during meiosis relies on the formation of double-strand DNA breaks (DSBs) and repair of a subset of these DSBs as inter-homolog crossovers (COs). Because the DSBs that serve as the initiating events of meiotic recombination pose a danger to genome integrity, the success of genome inheritance during meiosis requires cells to maintain a balance between the beneficial effects of COs and the potential harmful consequences of the process by which they are generated. A major goal of our research is to understand the mechanisms that operate during meiosis to achieve this crucial balance. An inter-related goal is to understand how meiosis-specific chromosome organization is established, maintained, and remodeled to bring about successful segregation of homologous chromosomes. We are approaching these issues using Caenorhabditis nematodes, simple metazoan organisms that are especially amenable to an integrated application of powerful cytological, genetic, genomic, and biochemical approaches, and in which the events under study are particularly accessible. Our goal under the MIRA program is to pursue a systems-level understanding of meiosis, based on the recognition that multiple distinct aspects of the meiotic program are intimately interconnected, and that robustness of the system is an emergent property of this interconnectedness. Our approach will build on recent technical advances and new discoveries in the well-established C. elegans experimental system, in combination with opportunities afforded by a newly-introduced Caenorhabditis interspecies hybrid model, to interrogate the meiotic program at multiple levels. Planned areas of investigation will include: Elucidating mechanisms that ensure reliable formation of CO- based connections for all chromosome pairs; Exploring how different events and developmental transitions in the meiotic program are temporally and spatially coordinated; Investigating the functional organization of meiosis-specific chromosome structures that promote and regulate meiotic recombination and enable chromosomes to sense and respond to events occurring at distant positions; Pursuing a new approach aimed at understanding the fundamental basis of homolog recognition.