Identifying and Characterizing Genetic Interactors of DMC1

智力优势：减数分裂，为受精做准备的基因组的还原分裂，是一个关键的生物学过程。 在减数分裂过程中，同源染色体相互作用，通过同源染色体之间的相互交换，如交换和基因转换，导致DNA的遗传重排。 在大多数真核生物中，这些事件确保正确的染色体分离，促进DNA修复，并为遗传多样性提供基础。 分子遗传学家在理解基础重组机制方面取得了实质性进展，其中大部分在酵母、植物和哺乳动物等多种生物体中是保守的。 因此，详细的模型描述的重组机制已被提出。 在大多数生物体中，这些机制中的关键蛋白质是DMC 1，它介导重组过程中同源染色体之间物理连接的建立。 在几种模式生物中对DMC 1的强烈关注表明，其活性受到许多介体蛋白的密切调节。 虽然DMC 1或类似的蛋白质（RecA同源物）在细菌，真菌，植物和动物等多种生物体中发现，但它们的介质并不保守。 事实上，模式植物拟南芥在芽殖酵母酿酒酵母（Saccharomycescerevisiae）中，只有四种蛋白质被提出来调节DMC 1。 作为这个项目的前奏，已经确定了10个突变体（抑制子），可能与拟南芥DMC 1相互作用。 了解与DMC 1相互作用的蛋白质（被鉴定为DMC 1突变体的抑制子）将能够描述植物用于介导减数分裂重组的机制。 此外，扩大我们对植物减数分裂重组的理解，有可能推进植物生物技术，包括我们通过利用重组来设计植物基因组的能力。更广泛的影响：该项目将为来自服务不足社区的年轻科学家参与尖端研究创造机会。 此外，PI将继续参与并开发一个针对高级本科生，研究生和博士后的课程，专门关注减数分裂和重组-这个课程是作为先前NSF奖项的更广泛影响力的一部分而发起的。

Intellectual Merit: Meiosis, the reductive division of the genome in preparation for fertilization, is a critical biological process. During meiosis, homologous chromosomes interact resulting in the heritable rearrangement of DNA through reciprocal exchange between homologous chromosomes by processes referred-to as crossing over and gene conversion. In most eukaryotes, these events ensure proper chromosome segregation, facilitate DNA repair, and provide a basis for genetic diversity. Molecular geneticists have made substantial progress in understanding the basal recombination machinery, much of which is conserved in organisms as diverse as yeast, plants and mammals. As a result, detailed models describing recombination mechanisms have been proposed. In most organisms, a key protein in these mechanisms is DMC1, which mediates the establishment of physical linkages between homologous chromosomes during recombination. Intense focus on DMC1 in several model organisms has revealed that its activity is closely regulated by a host of mediator proteins. While DMC1 or similar proteins (RecA homologs) are found in organisms as diverse as bacteria, fungi, plants and animals, their mediators are not as well conserved. Indeed, the model plant Arabidopsis thaliana shares only four of the ten proteins proposed to regulated DMC1 in the budding yeast Saccharomyces cerevisiae. As a prelude to this project, ten mutants (suppressors) have been identified that may interact with Arabidopsis DMC1. Understanding the proteins that interact with DMC1 (identified as suppressors of dmc1 mutants) will enable the description of the mechanisms that plants use to mediate meiotic recombination. In addition, expanding our understanding of plant meiotic recombination has the potential for advancing plant biotechnology including our ability to engineer plant genomes by harnessing recombination.Broader Impacts: The project will create opportunities for participation in cutting-edge research by young scientists from under-served communities. In addition, the PI will continue to participate in and develop a class for advanced undergraduates, graduates, and postdocs that focuses specifically on meiosis and recombination - this class was initiated as part of the broader impact efforts from a prior NSF award.