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: 6627242
• 负责人: PAUL Connor MEGEE
• 金额: $ 33.25万
• 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 2004-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6627242
• 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.

端粒是形成真核生物末端的DNA-蛋白质复合物 线性染色体并保护其完整性。 端粒是焦点 衰老研究（伴随着端粒逐渐丧失）和 肿瘤发生（需要端粒长度的稳定）。 最近的 研究表明端粒可能在有性生殖中发挥作用 好吧，因为它们与主轴极体（SPB）相关联并且 导致裂殖酵母减数分裂前阶段的染色体运动。 裂殖酵母端粒蛋白 Taz1 是端粒的关键调节因子 长度、结构和位置影响，但对于生存能力至关重要 仅存在于已启​​动性周期的细胞中。 事实上，Taz1p 是 SPB 处减数分裂前端粒聚类所需的，缺乏 这导致异常的减数分裂重组和分离。 塔兹1p 是第一个被证明参与端粒-SPB 关联的蛋白质 从而为研究其机制提供了前所未有的立足点 潜在的减数分裂染色体重排及其作用 性发育的重新安排。 拟议的工作涉及五个 问题，利用细胞学、分子遗传学和生理学 方法：（1）SPB 中端粒聚集的作用是什么？ 减数分裂以及哪些过程取决于减数分裂前染色体排列？ (2) 信息素反应产生哪些信号？ 减数分裂前染色体重排？ (3) 在什么条件下 Taz1p 对于有丝分裂生长很重要，它在这种情况下发挥什么作用 状况？ (4) 作为 2 和 3 的推论，Taz1p 是否受调控 磷酸化？ (5)哪些蛋白质与Taz1p相互作用来介导或 参与其减数分裂功能？ 这些研究将大大拓展 我们对有性生殖期间和有性生殖期间端粒功能的了解 压力。 鉴于已观察到减数分裂期间端粒聚集 在许多真核生物中，人类端粒蛋白 hTRF1 是 这些研究在结构和功能上与Taz1p同源 还阐明了人类减数分裂的过程。