Structure and dynamics of meiotic chromosomes

减数分裂期间的染色体分离将一条染色体，无论是母本还是父本， 每个配子遗传物质的精确分离需要亲本染色体与 通过杂交的形成互相交换遗传信息。交叉编队 需要染色体经历一系列精心安排的形态转变。未能做出 交叉导致减数分裂染色体分离错误，从而导致不育和先天性 出生缺陷这里提出的研究将使用线虫和芽殖酵母来解决机制 染色体的相互作用和分离，采用实验方法，利用 这些模型系统的独特功能，包括活体动物染色体动力学的直接成像。 允许染色体形成、调节和对交叉反应的分子机制很差 明白该建议探讨了减数分裂染色体的组织和动力学的三个方面。第一 该项目将探讨突触复合体（SC）-一种保守的结构， 同源染色体，并调节交叉的分布-实现染色体范围内 调控这项工作建立在最近的理解，SC，尽管其有序的外观时， 通过电子显微镜观察，是液体样相分离的隔室。一种新的诱变剂， 遗传筛选策略将分离干扰细胞液体性质的功能分离突变， SC，并以这种方式将特定功能分配给SC组件。此外，对染色体的了解甚少- 广泛的SC动态将首次使用长期实时成像直接可视化。一种机械的 对这些动力学的理解将解释减数分裂程序如何响应核型异常， 以及SC如何调节和响应交叉。 第二个项目的重点是重组的染色体，转换交叉-一个本地 DNA链的交换--进入连接，在交配过程中将亲本染色体保持在一起。 减数分裂，并促进其正确分离成配子。一种新颖的方式来标记只有一个 两个亲本染色体，并在整个减数分裂过程中可视化其形态将依赖于有利的 C.染色体的组织。和超分辨率显微镜的研究。 第三个项目是关于减数分裂染色体的组织， 在它们的基部延伸到蛋白质轴。这种保守的染色体组织是减数分裂的组成部分。 程序，但调节其组装和动力学的机制仍然是个谜。一种新的技术来 获得一个高分辨率的描述染色体构象和动态的芽殖酵母将采取 这是一项新兴技术的优势，可以对非常长的DNA分子进行测序。这种技术可以 广泛应用于探测其他细胞过程中的染色体组织。

Chromosome segregation during meiosis places one chromosome, either the maternal or paternal copy, in each gamete. Accurate segregation of genetic material requires that the parental chromosomes interact with one another and exchange genetic information through the formation of crossovers. Crossover formation requires that chromosomes undergo an orchestrated series of morphological transformations. Failure to make crossovers leads to errors in meiotic chromosome segregation, and consequently to infertility and congenital birth defects. The research proposed here will use nematodes and budding yeast to address the mechanisms of chromosome interaction and segregation by employing experimental approaches that take advantage of the unique features of these model systems, including direct imaging of chromosome dynamics in living animals. The molecular mechanisms that allow chromosomes to form, regulate, and respond to crossovers are poorly understood. This proposal probes three aspects of meiotic chromosome organization and dynamics. The first project will explore how the Synaptonemal Complex (SC)—a conserved structure that assembles between homologous chromosomes and regulates the distribution of crossovers—implements chromosome-wide regulation. This work builds on the recent understanding that the SC, despite its ordered appearance when visualized by electron microscopy, is a liquid-like phase-separated compartment. A novel mutagenesis and genetic screening strategy will isolate separation-of-function mutations that perturb the liquid properties of the SC, and in that way assign specific functions to SC components. In addition, poorly understood chromosome- wide SC dynamics will be directly visualized for the first time using long-term live-imaging. A mechanistic understanding of these dynamics will explain how the meiotic program responds to karyotype abnormalities, and how the SC regulates, and responds to, crossovers. The second project focuses on the reorganization of the chromosomes that transforms crossovers—a local exchange of DNA strands—into the connections that hold the parental chromosomes together during the meiotic divisions, and promotes their correct segregation into gametes. A novel way to label only one of the two parental chromosomes and to visualize its morphology throughout meiosis will rely on the advantageous organization of chromosomes in the C. elegans gonad and on super-resolution microscopy. The third project addresses the organization of meiotic chromosomes as loops of chromatin that are anchored at their base to a proteinaceous axis. This conserved chromosome organization is integral to the meiotic program, but the mechanisms regulating its assembly and dynamics remain enigmatic. A novel technique to obtain a high-resolution description of chromosome conformation and dynamics in budding yeast will take advantage of an emerging technology to sequence very long molecules of DNA. This technique could be widely applied to probe chromosome organization in other cellular processes.