Molecular analysis of genome stability/meiosis

基因组稳定性/减数分裂的分子分析

• 批准号: 5395-2009
• 负责人: Pearlman, Ronald
• 金额: $ 4.37万
• 依托单位: York University
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2011
• 资助国家: 加拿大
• 起止时间: 2011-01-01 至 2012-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=473959
• 关键词: Molecular; analysis; genome; stability; meiosis

Ciliated protozoa such as Tetrahymena thermophila are characterized by having two nuclei in the same cell. The polyploid macronucleus (MAC) functions as the cell's somatic nucleus. The diploid micronucleus (MIC) is the cell's germinal nucleus. The MIC undergoes the special cell division called meiosis in this useful and much exploited animal model system. This proposal focuses on molecular studies of meiosis approached from the perspective of genome stability. Some of the areas of focus in this proposal are: 1) Meiosis in Tetrahymena is unusual in two important aspects; there is no synaptonemal complex (SC), a structure generally associated with the highly conserved process of meiosis; and, the elongated crescent structure of chromosomes in meiotic prophase I is very unusual. One can often learn more from studying differences in evolutionarily conserved processes rather than similarities so this system provides a powerful paradigm to address important questions about meiosis. 2) Genome stability is important for the life of an organism. Problems with genome stability can lead to problems including diseases. We will study genome stability through double strand break (DSB) repair. Relationships between DSB repair and DSBs in meiosis will be addressed. 3) DNA in a cell is organized as chromatin, i.e. it is associated with specific small, basic proteins called histones. Histone release and histone deposition is an important aspect of DNA replication. We will address questions about histone deposition focusing on DSB repair and on meiosis. 4) It has been thought that signaling by tyrosine phosphorylation was restricted to multicellular organisms. Recently, evidence has been presented that this pathway exists in unicellular eukaryotes. We have identified a novel tyrosine signaling pathway induced during cell pairing and early stages of mating in Tetrahymena. This study will have important implications for the evolution and function of tyrosine phosphorylation signaling in development. These studies using an exceptionally useful and versatile animal model organism provide important opportunities to train HQP studying important problems and using and developing state-of-the-art technologies.

纤毛原生动物（例如嗜热四膜虫）的特征是在同一细胞中具有两个细胞核。多倍体大核（MAC）充当细胞的体细胞核。二倍体微核（MIC）是细胞的生发核。在这个有用且被广泛利用的动物模型系统中，MIC 经历称为减数分裂的特殊细胞分裂。该提案侧重于从基因组稳定性角度进行减数分裂的分子研究。该提案的一些重点领域是： 1）四膜虫的减数分裂在两个重要方面是不寻常的；不存在联会复合体（SC），这种结构通常与高度保守的减数分裂过程相关；而且，减数分裂前期 I 中染色体拉长的新月形结构非常不寻常。人们通常可以通过研究进化保守过程的差异而不是相似性来了解更多信息，因此该系统提供了一个强大的范例来解决有关减数分裂的重要问题。 2）基因组稳定性对于生物体的生命很重要。基因组稳定性问题可能导致包括疾病在内的问题。我们将通过双链断裂（DSB）修复来研究基因组稳定性。 DSB 修复和减数分裂中 DSB 之间的关系将得到解决。 3) 细胞中的 DNA 以染色质的形式组织，即它与称为组蛋白的特定小碱性蛋白质相关。组蛋白释放和组蛋白沉积是DNA复制的重要方面。我们将解决有关组蛋白沉积的问题，重点是 DSB 修复和减数分裂。 4) 人们认为酪氨酸磷酸化信号传导仅限于多细胞生物。最近，有证据表明该途径存在于单细胞真核生物中。我们发现了四膜虫细胞配对和交配早期阶段诱导的新型酪氨酸信号通路。 这项研究将对发育过程中酪氨酸磷酸化信号的进化和功能产生重要影响。这些使用极其有用且多功能的动物模型生物体的研究为培训 HQP 研究重要问题以及使用和开发最先进的技术提供了重要的机会。