Mechanisms of meiotic and mitotic recombination

减数分裂和有丝分裂重组机制

基本信息

批准号：
10593114
负责人：
JEFF J. SEKELSKY
金额：
$ 54.48万
依托单位：
UNIV OF NORTH CAROLINA CHAPEL HILL
依托单位国家：
美国
项目类别：
财政年份：
2016
资助国家：
美国
起止时间：
2016-06-01 至 2026-03-31
项目状态：
未结题

项目摘要

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.

抽象的重组既是避免基因组不稳定的一种方法，也是处理产生基因组不稳定的方法。在减数分裂中，DNA 双链断裂被修复为交叉，这对于准确的预测至关重要。同源染色体的分离；该过程中的缺陷会导致不育或非整倍体，这是主要的流产和三体性的原因。相反，在有丝分裂增殖的细胞中，双链断裂是危险类别的 DNA 损伤。在这种情况下，修复断裂是在不进行交叉的情况下完成的；有丝分裂细胞中交叉的形成可导致染色体重排和肿瘤发生。我实验室的研究重点是促进减数分裂细胞和非减数分裂细胞交叉的机制。有丝分裂细胞修复的交叉结果。我们为理解这些做出了重要贡献 20年来，我培养了许多活跃于研究和研究领域的科学家。研究相关的职业。该提案勾勒出持续的和新的方向，将推动场向前。其中包括研究如何修复大间隙（对于设计 Cas9 很重要）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进行的有图案（对于将染色体正确分离成配子很重要）。我们使用组合遗传学，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，进化论生物学和数学建模。