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.

研究摘要 需要染色体之间的重组以产生遗传变异，维持基因组完整性 通过修复双链DNA断裂（DSB），并确保在 减数分裂，专门的细胞分裂程序，二倍体生物会产生单倍体游戏，例如 精子和鸡蛋。重组中的扰动会损害这些基本的细胞函数，最终 导致癌症，不育或出生缺陷。减数分裂重组是由DSB启动的，该重组已修复 使用有利用同源染色体的减数分裂特异性机制（而不是姐妹） 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的维修 适当的模板（同类染色体）对于适当的染色体隔离和 基因组完整性，我们对生殖细胞如何实现此模板偏好的了解 几乎相同的序列（姐妹染色单体）是有限的。使用秀丽隐杆线虫作为模型系统，我们 已经开发了一种荧光测定，以监测诱导的DSB的维修，并在 减数分裂预言在体内的进展。资助赠款的主要目标之一是使用此测定法 确定如何调节这些不同的维修伙伴选择。为我们种植秀丽隐杆线 实验，我们需要具有微调温度控制的孵化器。该补充将支持 购买一个孵化器来替换我们的15°C孵化器突然破裂而没有 可用的替换零件。总体而言，要求的孵化器更换对于我们的研究至关重要 计划并将使我们能够实现我们的目标，以确定分子特征，染色体特征， 以及与维持基因组完整性至关重要的这些不同修复结果相关的蛋白质 在精子和卵发育期间。