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: 6343073
• 负责人: JULIA S COOPER
• 金额: $ 31.36万
• 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/6343073
• 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DNA-蛋白质复合物，形成真核生物的末端。 线性染色体并保护其完整性。 端粒是一个焦点 对衰老（伴随着端粒的逐渐丧失）的研究， 肿瘤发生（需要稳定端粒长度）。 最近 这项研究表明，端粒可能在有性生殖中发挥作用， 好吧，当它们与纺锤体（SPB）相关联时， 在分裂酵母减数分裂前阶段导致染色体运动。 裂殖酵母端粒蛋白Taz 1是端粒的关键调节因子 长度、结构和位置的影响，但对生存能力至关重要 只在启动性周期的细胞中。 事实上，Taz 1 p是 所需的减数分裂前端粒聚集在SPB，缺乏 导致异常的减数分裂重组和分离。 Taz1p 是第一个参与端粒-SPB关联的蛋白质 从而为研究这些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和这些作用 性发育的重组。 建议的工作涉及五个 问题，使用细胞学，分子遗传学和生理学 方法：（1）端粒在SPB聚集的作用是什么？ 减数分裂和什么过程取决于减数分裂前染色体排列？ (2)什么是信号，导致从信息素的反应， 减数分裂前染色体重排(3)在什么条件下 Taz 1 p对有丝分裂生长很重要，在这种情况下它起什么作用？ 条件？(4)作为2和3的推论，Taz 1 p是否受 磷酸化？(5)什么蛋白质与Taz 1 p相互作用来介导或 参与减数分裂的功能 这些研究将大大扩展 我们对端粒在有性生殖过程中的功能以及 应力 考虑到减数分裂过程中端粒的卷曲已经被观察到， 在许多真核生物中，人类端粒蛋白hTRF 1是 在结构和功能上与Taz 1 p同源，这些研究应该 也阐明了人类减数分裂的过程。