Molecular Control of Meiotic Chromosome Dynamics

减数分裂染色体动力学的分子控制

• 批准号: 9382185
• 负责人: Yumi Kim
• 金额: $ 40.88万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-09-01 至 2022-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9382185
• 关键词: Aneuploidy; Biochemical; Caenorhabditis elegans; Cell Cycle Regulation; Cell division; Cells; Chromatin Loop; Chromosome Segregation; Chromosomes; Congenital Abnormality; Down Syndrome; Event; Fertilization; Genetic; Genetic Recombination; Genetic study; Genome; Germ Cells; Haploidy; Human; Lead; Malignant Neoplasms; Meiosis; Molecular; Organism; Parents; Process; Production; Proteins; Public Health; Research; Spontaneous abortion; Synapses; Work; chromosome number abnormality; egg; offspring; programs; sperm cell; zygote

Project Summary/Abstract Sexually reproducing organisms rely on meiosis, a specialized cell division that produces haploid gametes such as sperm and eggs, to restore the genetic content of the zygote through fertilization. Errors in this process lead to the production of offspring with an abnormal number of chromosomes or aneuploidy, and this is a major cause of human miscarriages and birth defects such as Down syndrome. Accurate segregation of chromosomes during meiosis requires that they pair, synapse, and undergo crossover recombination with their homologs. Although genetic studies over the decades have identified a list of proteins that are essential for meiotic processes, it remains largely unknown how these protein machines work together to orchestrate chromosome dynamics. My research program will investigate these fundamental processes by combining biochemical and structural analysis using purified components, with the ability to examine meiosis in the context of highly tractable C. elegans germline. Early in meiosis, chromosomes are dramatically reorganized into arrays of chromatin loops tethered to a proteinaceous axis, and this is essential for all major meiotic events

项目总结/摘要 有性繁殖的生物体依靠减数分裂，一种产生单倍体配子的特殊细胞分裂 例如精子和卵子，通过受精恢复受精卵的遗传内容。此过程中的错误 导致产生染色体数目异常或非整倍体的后代，这是一个主要的 导致人类流产和唐氏综合症等出生缺陷的原因。精确分离 染色体在减数分裂过程中需要配对，突触，并进行交叉重组与他们的 同系物。尽管几十年来的遗传学研究已经确定了一系列蛋白质，这些蛋白质对 减数分裂过程中，仍然很大程度上不知道这些蛋白质机器如何协同工作， 染色体动力学我的研究计划将通过结合这些基本过程来研究这些基本过程。 使用纯化的组分进行生物化学和结构分析，具有检查减数分裂的能力。 高度可处理的上下文C.秀丽隐杆线虫生殖系在减数分裂的早期， 形成一系列连接在蛋白质轴上的染色质环，这对所有主要的减数分裂都是必不可少的。 事件