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: 6138714
• 负责人: JULIA S COOPER
• 金额: $ 27.82万
• 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/6138714
• 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-蛋白质复合体。 线性染色体并保护它们的完整性。端粒是一个焦点 关于衰老的研究(伴随着逐渐的端粒丢失)和 肿瘤的发生(这需要稳定的端粒长度)。近期 研究表明，端粒可能在有性繁殖中发挥作用， 当它们与主轴极体(SPB)和 裂殖酵母减数分裂前阶段的铅染色体运动。 裂解酵母端粒蛋白Taz1是端粒的关键调控因子 长度、结构和位置效应，但对生存能力至关重要 只存在于启动了性周期的细胞中。事实上，Taz1p是 SPBS的减数分裂前端粒聚集所需的 这会导致减数分裂的异常重组和分离。Taz1p 是第一个参与端粒-SPB联系的蛋白质吗？ 从而为研究这一机制提供了前所未有的立足点 减数分裂染色体重排的基础及其作用 性发育中的重新安排。拟议的工作涉及五个方面 问题，使用细胞学、分子遗传学和生理学 方法：(1)端粒聚集在SPBS中的作用是什么 减数分裂和哪些过程依赖于减数分裂前的染色体对齐？ (2)信息素反应产生的信号是什么？ 减数分裂前染色体重排？(3)在什么条件下 Taz1p对有丝分裂的生长很重要，在这种情况下它扮演着什么角色 条件？(4)作为2和3的推论，Taz1p是否受 磷酸化？(5)哪些蛋白质与Taz1p相互作用，介导或 参与其减数分裂功能？这些研究将大大扩展 我们对有性生殖过程中端粒功能的了解 压力。鉴于已经观察到减数分裂过程中端粒的生长 在许多真核生物中，人类端粒蛋白hTRF1 这些研究在结构和功能上与Taz1p同源 还阐明了涉及人类减数分裂的过程。