Centromere Interactions and Meiotic Chromosome Segregation in Yeast

酵母着丝粒相互作用和减数分裂染色体分离

• 批准号: 10210732
• 负责人: DEAN S DAWSON
• 金额: $ 34.96万
• 依托单位: OKLAHOMA MEDICAL RESEARCH FOUNDATION
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-04-01 至 2024-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10210732
• 关键词: Anaphase; Aneuploidy; Behavior; Behavior monitoring; Cells; Centromere; Chromatin; Chromosome Pairing; Chromosome Segregation; Chromosomes; Congenital Abnormality; Distal; Distant; Drosophila genus; Ensure; Failure; Genetic Crossing Over; Germ Cells; Human; Infertility; Lead; Link; Measures; Mediating; Meiosis; Mental Retardation; Metaphase; Microscopy; Microtubule Stabilization; Microtubules; Modeling; Monitor; Mus; Positioning Attribute; Process; Prometaphase; Property; Prophase; Proteins; S Phase; Saccharomycetales; Side; Signal Pathway; Signal Transduction; Sister Chromatid; System; Testing; Work; Yeasts; biophysical techniques; chromosome movement; cohesin; cohesion; experience; experimental study; improved; live cell imaging; mutant; prevent; segregation

Project Summary Homologous chromosomes enter meiosis unconnected to each other, but they become linked by crossovers (exchanges). These linkages help the homologous chromosomes to move away from each other in meiosis I. The linkages transmit tension between the homologous centromeres when they become attached to microtubules from opposite sides of the spindle (bi-oriented). Tension stabilizes these microtubule attachments. Accordingly, failures in crossing-over can result in meiotic errors and aneuploid gametes. The pairing of homologous centromeres (CEN-pairing) in meiotic prophase, is a recently discovered, conserved phenomenon. In yeast, CEN-pairing helps the partner chromosomes, later, in anaphase I, to segregate properly, even if they have failed to experience a crossover. The mechanism by which CEN-pairing promotes segregation is unknown. While crossover formation has been investigated for decades, very little is known about how CEN-pairing promotes meiotic chromosome segregation. This is the focus of our proposal. In Aim 1 we test the hypothesis that the CEN-pairing allows the formation of centromere-centromere connections that improve the segregation fidelity of meiotic chromosome partners. We will use live cell imaging to monitor the meiotic behavior of chromosome pairs have or have not undergone CEN-pairing. In Aim 2 we will test the hypothesis that connections formed during CEN-pairing are mediated by cohesin proteins. Aim 3 will explore mechanism by which centromere-centromere connections help partner chromosomes become bi-oriented on the spindle. We will directly measure the spring-like properties of the centromere-to-centromere connections using bio-physical approaches and test whether partners with a centromere-centromere connection can use the tension-sensing signaling pathways. In addition, these experiments will test the hypothesis that centromere-centromere connections are important to improve the segregation fidelity of chromosome pairs linked by crossovers that alone would be ineffective in creating a tension-transmitting bridge as the pair attaches to microtubules. Together, the experiments in this project will elucidate the reasons that some crossovers do, and some don’t, effectively ensure high fidelity chromosome segregation in meiosis and will explain how the recently described process of centromere pairing can mediate the formation of a centromere- to-centromere connection between homologs that augments the functionality of crossovers, or can act alone when crossovers fail.

项目摘要 同源染色体彼此之间无关的减数分裂，但它们与 交叉（交换）。这些连接有助于同源染色体在 减数分裂I.链接在依恋与 微管来自主轴的相对侧（面向双向）。张力稳定这些微管 附件。根据确定，越过的失败会导致减数分裂错误和非整倍性游戏。 减数分裂预言中的同源centromos Centromeres（CEN配对）是最近发现的保守的 现象。在酵母中，CEN配对有助于伴侣染色体，后来在后期I中隔离 正确地，即使他们没有经历过跨界。 CEN配对促进的机制 隔离是未知的。虽然已经研究了数十年的跨界形成，但鲜为人知 关于CEN配对如何促进减数分裂染色体的分离。这是我们建议的重点。目标 1我们检验了CEN配对允许形成Centromere-Centromere连接的假设 改善减数分裂染色体伴侣的隔离保真度。我们将使用活细胞成像监视 染色体对的减数分裂行为具有或未经过CEN配对。在AIM 2中，我们将测试 CEN配对过程中形成的连接的假设是由粘蛋白蛋白介导的。 AIM 3将探索 Centromere-Centromere连接有助于伴侣染色体的机制，以双向为导向 主轴。我们将直接测量着丝粒到中心连接的春季样性能 使用生物物理方法，并测试与中心中心连接的合作伙伴是否可以使用 张力感应信号通路。此外，这些实验将检验以下假设。 Centromere-Centromere连接对于改善染色体对的隔离保真度很重要 由单独的跨界链接起来，这些跨界将无效地创建张力传递桥 附着于微管。共同进行该项目的实验将阐明某些原因 分频器确实有效地确保减数分裂中的高保真染色体隔离 说明最近描述的中心粒配对过程如何介导centromere-的形成 同源物之间增强交叉功能或可以单独行动的同源物之间的中心连接 当跨界失败时。