Isolation and characterization of C.elegans meiotic mutants - regulation of chromosome association dynamics during meiosis

线虫减数分裂突变体的分离和表征 - 减数分裂过程中染色体关联动态的调节

• 批准号: 401960-2011
• 负责人: EgydiodeCarvalho, Carlos
• 金额: $ 2.55万
• 依托单位: University of Saskatchewan
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2017
• 资助国家: 加拿大
• 起止时间: 2017-01-01 至 2018-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=629621
• 关键词: Isolation; characterization; C.elegans; meiotic; mutants

The tight control of chromosome association and dissociation during cell division ensures the viability of daughter cells. In meiosis, chromosomes separate in two steps such that first homologs segregate in meiosis I and later sister chromatids disjoin in meiosis II. To avoid the sudden separation of sister chromatids already in meiosis I and subsequent collapse of cell division, cohesion proteins must not be completely removed from meiosis I chromosomes. Eukaryotic cells accomplish that by differentially protecting subsets of cohesion proteins on chromosomes from the activity of separase, an enzyme required to break chromosomal links. By selectively protecting cohesion proteins, meiotic cells can sustain sister chromatid association past homolog segregation. This protection of cohesion has been correlated with the presence of the centromere, the connecting point between sister chromatids and a center hub from where chromosomes attach to the spindle. However, a whole set of animal and plant species have cells whose chromosomes do not have a classic centromere. Nonetheless, protection of chromosome cohesion in these organisms still needs to occur. The main objective of the research program is to investigate how protection of cohesion is regulated in this alternative chromosome architecture. To address this problem, meiosis in the nematode C.elegans, whose chromosomes lack centromeres, will be used to identify new genes necessary for the proper segregation of meiotic chromosomes. By utilizing genetic and molecular tools, this research will provide us with a better picture on how the mechanisms regulating chromosome separation evolved and help understand the precise role of the centromere in this process. Aside from chromosome biology and evolution, results from this research will impact the study of cell cycle regulators and provide a platform for future research on organisms whose chromosomes lack a defined centromere.

细胞分裂过程中对染色体结合和解离的严格控制确保了子代细胞的活性。在减数分裂过程中，染色体分两步分离，首先同源染色体在减数分裂I中分离，然后姐妹染色单体在减数分裂II中分离。为了避免已经在减数分裂I中的姐妹染色单体突然分离和随后的细胞分裂崩溃，不能从减数分裂I染色体上完全去除凝聚蛋白。真核细胞通过不同地保护染色体上的凝聚蛋白亚群不受分离酶的影响来实现这一点，分离酶是断开染色体连接所需的一种酶。通过选择性地保护凝聚力蛋白，减数分裂细胞可以在同源分离后维持姐妹染色单体关联。这种凝聚力的保护与着丝粒的存在有关，着丝粒是姐妹染色单体之间的连接点，也是染色体与纺锤体相连的中心枢纽。然而，一整套动植物物种的细胞的染色体并没有典型的着丝粒。尽管如此，对这些生物的染色体凝聚力的保护仍然需要发生。该研究计划的主要目的是调查如何在这种可选的染色体结构中调节凝聚力的保护。为了解决这个问题，线虫的减数分裂，其染色体缺乏着丝粒，将被用来识别减数分裂染色体适当分离所需的新基因。通过利用遗传和分子工具，这项研究将为我们提供更好的图像，了解调控染色体分离的机制是如何演变的，并有助于理解着丝粒在这一过程中的确切作用。除了染色体生物学和进化，这项研究的结果将影响细胞周期调节的研究，并为未来对染色体缺乏明确着丝粒的生物的研究提供平台。