TELOMERE FUNCTION DURING MEIOSIS IN FISSION YEAST

裂殖酵母减数分裂过程中的端粒功能

• 批准号: 6490180
• 负责人: PAUL Connor MEGEE
• 金额: $ 32.3万
• 依托单位: UNIVERSITY OF COLORADO DENVER
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-01-01 至 2003-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6490180
• 关键词: biological signal transduction; chemical structure function; chromosome movement; flow cytometry; fluorescence microscopy; fungal genetics; meiosis; nucleoproteins; pheromone; phosphorylation; protein protein interaction; reproduction; spindle pole body; telomere; yeast two hybrid system; yeasts

Telomeres are the DNA-protein complexes that form the ends of eukaryotic linear chromosomes and protect their integrity. Telomeres are a focus of research on aging (which is accompanied by gradual telomere loss) and tumorigenesis (which requires stabilization of telomere length). Recent work suggests that telomeres might play roles in sexual reproduction as well, as they become associated with the spindle pole bodies (SPBs) and lead chromosome movements during pre-meiotic stages in fission yeast. The fission yeast telomere protein Taz1 is a key regulator of telomere length, structure and position effects, but is critical for viability only in cells that have initiated the sexual cycle. Indeed, Taz1p is required for pre-meiotic telomere clustering at the SPBs, the absence of which leads to aberrant meiotic recombination and segregation. Taz1p is the first protein shown to be involved in telomere-SPB associations and thus provides an unprecedented foothold for studying the mechanisms underlying meiotic chromosomal rearrangements and the roles of these rearrangements in sexual development. The proposed work addresses five questions, using cytological, molecular genetic, and physiological approaches: (1) What is the role of telomere clustering at SPBs during meiosis and what processes depend on pre-meiotic chromosomal alignment? (2) What are the signals that lead from the pheromone response to the pre-meiotic chromosomal rearrangements? (3) Under what conditions is Taz1p important for mitotic growth and what role does it play under such conditions? (4) As a corollary to 2 and 3, is Taz1p regulated by phosphorylation? (5) What proteins interact with Taz1p to mediate or participate in its meiotic function? These studies will greatly expand our knowledge of telomere function during sexual reproduction and under stress. Given that telomere culstering during meiosis has been observed in many eukaryotes, and that the human telomere protein hTRF1 is structurally and functionally homologous to Taz1p these studies should also illuminate processes involved in human meiosis.

端粒是构成真核末端的DNA蛋白质复合物 线性染色体并保护其完整性。 端粒是重点 衰老研究（伴随着逐渐端粒损失）和 肿瘤发生（需要稳定端粒长度）。 最近的 工作表明，端粒可能在有性繁殖中发挥作用 好吧，随着它们与主轴杆体（SPB）相关联 在裂变酵母中，脂肪体阶段期间的铅染色体运动。 裂变酵母端粒蛋白TAZ1是端粒的关键调节剂 长度，结构和位置效应，但对于生存能力至关重要 仅在启动性周期的细胞中。 确实，TAZ1P是 在SPB处进行求维生型端粒前聚类所必需的 其中导致了异常的减数分裂重组和隔离。 taz1p 是与端粒SPB关联有关的第一个蛋白质 因此，为研究机制提供了前所未有的立足点 减数分裂染色体的重排和这些作用 性发展的重排。 拟议的工作解决了五个 使用细胞学，分子遗传和生理学的问题 方法：（1）端粒聚类在SPB中的作用是什么 减数分裂和哪些过程取决于求生染色体前的一排列？ （2）从信息素响应到对的信号是什么 寿息前染色体重排？ （3）在什么条件下 TAZ1P对于有丝分裂生长很重要，并且在这种情况下起着什么作用 状况？ （4）作为2和3的推论，受TAZ1P的调节 磷酸化？ （5）哪些蛋白质与TAZ1P相互作用以介导或 参与其减数分裂功能？ 这些研究将大大扩展 我们对性繁殖期间端粒功能的了解 压力。 鉴于已经观察到减数分裂过程中的端粒尖端 在许多真核生物中，人端粒蛋白htrf1是 在结构和功能上与TAZ1P同源这些研究应 还阐明了与人类减数分裂有关的过程。