Mechanisms of meiotic and mitotic recombination

摘要 纯化既是避免基因组不稳定性的手段，也是产生基因组不稳定性的过程。 在减数分裂中，DNA双链断裂被修复成交叉，这对准确的DNA合成至关重要。 同源染色体的分离;在这个过程中的缺陷导致不育或非整倍体， 导致流产和三体性。相反，在有丝分裂增殖的细胞中，双链断裂是一个重要的因素。 危险的DNA损伤在这种情况下，不进行交叉就可以完成断裂的修复; 在有丝分裂细胞中形成交换可导致染色体重排和肿瘤发生。 我实验室的研究集中在促进减数分裂细胞和非减数分裂细胞中的交换的机制上。 有丝分裂细胞修复的交叉结果。我们做出了重要贡献， 20年来，我培养了许多活跃在研究领域的科学家， 与研究相关的职业。该提案概述了将推动 场向前。其中包括研究如何修复大的间隙（对于设计Cas9 片段整合实验和基于Cas9的基因驱动系统）以及减数分裂交叉是如何 模式化（对染色体正确分离成配子很重要）。我们结合使用 遗传学，主要使用果蝇作为模式生物，基因组学，生物化学，细胞生物学，进化 生物学和数学建模。

ABSTRACT Recombination is both a means to avoid genome instability and to process that generates genome instability. In meiosis, DNA double-strand breaks are repaired into crossovers that are essential for accurate segregation of homologous chromosomes; defects in this process result in sterility or aneuploidy, the major cause of pregnancy loss and trisomy. Conversely, in mitotically proliferating cells double-strand breaks are a dangerous class of DNA damage. Repair of breaks in this context is done without making crossovers; formation of crossovers in mitotic cells can lead to chromosome rearrangements and tumorigenesis. Research in my laboratory focuses on mechanisms that promote crossovers in meiotic cells and non- crossover outcomes of repair in mitotic cells. We have made important contributions to understand these problems for 20 years, during which time I have trained numerous scientists who are active in research and research-related careers. This proposal sketches out both continued and new directions that will drive the field forward. These include investigations of how large gaps are repaired (important for designing Cas9 fragment integration experiments and Cas9-based gene drive systems) and how meiotic crossovers are patterned (important for proper segregation of chromosomes into gametes). We use a combination of genetics, primarily using Drosophila as a model organism, genomics, biochemistry, cell biology, evolutionary biology, and mathematical modeling.