Recombination pathway and partner choices during meiosis

减数分裂过程中的重组途径和伴侣选择

• 批准号: 10335679
• 负责人: Diana Elizabeth Libuda
• 金额: $ 0.74万
• 依托单位: UNIVERSITY OF OREGON
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-02-01 至 2023-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10335679
• 关键词: Biological Assay; Biological Models; Caenorhabditis elegans; Cell division; Cell physiology; Chromosome Segregation; Chromosomes; Congenital Abnormality; DNA Double Strand Break; DNA Repair; Development; Diploidy; Emergency Situation; Ensure; Equipment; Event; Fertility; Funding; Genetic Recombination; Genetic Variation; Germ Cells; Goals; Grant; Haploidy; Health; Human; Incubators; Infertility; Knowledge; Malignant Neoplasms; Meiosis; Meiotic Recombination; Molecular Profiling; Monitor; Organism; Outcome; Pathway interactions; Process; Prophase; Proteins; Research; Sister Chromatid; Spontaneous abortion; Temperature; ds-DNA; egg; experimental study; genetic information; genome integrity; in vivo; preference; prevent; programs; repaired; sperm cell

Research Summary Recombination between chromosomes is required to generate genetic variation, maintain genome integrity through the repair of double strand DNA breaks (DSBs), and ensure proper chromosome segregation during meiosis, the specialized cell division program by which diploid organisms generate haploid gametes such as sperm and eggs. Perturbations in recombination can compromise these basic cellular functions, ultimately leading to cancer, infertility, or birth defects. Meiotic recombination is initiated by DSBs, which are repaired using meiosis-specific mechanisms that favor utilization of the homologous chromosome (instead of the sister chromatid) as the recombination partner and that promote a crossover outcome of the DSB repair process, which is required for promoting proper chromosome segregation during meiosis. Although repair of DSBs with the appropriate template (homologous chromosome) is necessary for proper chromosome segregation and genome integrity, our knowledge about how germ cells achieve this template preference in the presence of nearly identical sequences (sister chromatids) is limited. Using Caenorhabditis elegans as a model system, we have developed a fluorescent assay to monitor repair of an induced DSB with the sister chromatid during meiotic prophase progression in vivo. One of the primary goals of the funded grant is to use this assay to determine how these different repair partner choices are regulated. To grow the C. elegans for our experiments, we require incubators with fine tuned temperature control. This supplement will support the purchase of an incubator to replace our 15°C incubator that suddenly broke down and for which there are not replacement parts available. Overall, the requested incubator replacement is essential for our research program and will enable us to achieve our goals to identify the molecular signatures, chromosomal features, and proteins associated with these different repair outcomes that are central to maintaining genomic integrity during sperm and egg development.

研究总结 染色体之间的重组是产生遗传变异、维持基因组完整性所必需的 通过修复双链DNA断裂（DSB），并确保在过程中正确的染色体分离 减数分裂，二倍体生物体产生单倍体配子的专门细胞分裂程序，例如 精子和卵子重组过程中的扰动最终会损害这些基本的细胞功能。 导致癌症、不孕或出生缺陷的减数分裂重组是由 DSB 启动的，并被修复。 使用有利于利用同源染色体（而不是姐妹染色体）的减数分裂特异性机制 染色单体）作为重组伙伴并促进 DSB 修复过程的交叉结果， 虽然 DSB 的修复是在减数分裂过程中促进适当的染色体分离所必需的。 适当的模板（同源染色体）对于正确的染色体分离和 基因组完整性，我们关于生殖细胞如何在存在的情况下实现这种模板偏好的知识 使用秀丽隐杆线虫作为模型系统，几乎相同的序列（姐妹染色单体）是有限的。 开发了一种荧光测定法来监测诱导 DSB 与姐妹染色单体的修复 资助的主要目标之一是使用这种测定法来进行体内减数分裂前期进展。 确定如何监管这些不同的修复合作伙伴选择来为我们种植线虫。 实验中，我们需要具有微调温度控制的培养箱，该补充品将支持。 购买一台培养箱来替换我们突然故障且没有的 15°C 培养箱 总体而言，所需的培养箱更换对于我们的研究至关重要。 计划将使我们能够实现识别分子特征、染色体特征、 以及与这些不同修复结果相关的蛋白质，这些蛋白质对于维持基因组完整性至关重要 在精子和卵子发育过程中。