Molecular analysis of genome stability/meiosis

纤毛原生动物，如嗜热四膜虫，其特点是在同一个细胞中有两个细胞核。多倍体巨核（polyploid macronuclear， MAC）是细胞的体细胞核。二倍体微核（MIC）是细胞的生发细胞核。在这个有用的和被开发的动物模型系统中，MIC经历了称为减数分裂的特殊细胞分裂。本文主要从基因组稳定性的角度进行减数分裂的分子研究。本提案的一些重点领域是：1)四膜虫减数分裂在两个重要方面是不寻常的；没有突触复合体（synaptonemal complex， SC），这种结构通常与减数分裂的高度保守过程有关；在减数分裂前期，染色体呈细长的新月形结构是很不寻常的。人们通常可以从研究进化保守过程中的差异而不是相似性中学到更多，因此该系统为解决有关减数分裂的重要问题提供了强有力的范例。基因组的稳定性对生物体的生命至关重要。基因组稳定性的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）修复研究基因组的稳定性。探讨减数分裂中DSB修复与DSB之间的关系。细胞中的DNA是由染色质组成的，也就是说，它与被称为组蛋白的特定的小而基本的蛋白质有关。组蛋白释放和沉积是DNA复制的一个重要方面。我们将讨论组蛋白沉积的问题，重点是DSB修复和减数分裂。4)一直认为酪氨酸磷酸化的信号传导仅限于多细胞生物。最近，有证据表明这一途径存在于单细胞真核生物中。我们已经确定了一种新的酪氨酸信号通路诱导在细胞配对和交配的早期阶段在四膜虫。该研究将对酪氨酸磷酸化信号在发育中的进化和功能具有重要意义。这些研究使用了一种非常有用和通用的动物模式生物，为训练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机会。

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.