MECHANISM(S) CONTROLLING GROWTH/MEIOSIS SWITCH IN YEAST

酵母中控制生长/减数分裂转换的机制

• 批准号: 6417162
• 负责人: SAUL M HONIGBERG
• 金额: $ 6.74万
• 依托单位: UNIVERSITY OF MISSOURI KANSAS CITY
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-08-01 至 2003-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6417162
• 关键词: DNA replication; biological signal transduction; cell differentiation; cell growth regulation; chromosome movement; cyclins; fungal genetics; genetic manipulation; genetic regulation; meiosis; nutrition; yeasts

The switch between differentiation and growth is precisely regulated in all organisms. Loss of this control in humans can lead to cancer. Differentiation/growth switches are generally controlled by multiple extracellular signals, but analyzing the relationship between different controls is difficult in most systems. A simple prototype exists in diploid yeast, where three different types of control (cell cycle, glucose and acetate interact to regulate the switch between growth and meiosis. Yeast genetics provides a powerful tool for analyzing these different layers of control both separately and in combination. A central feature of growth/differentiation switches is that the two programs are mutually exclusive: cells must shut down one program to undergo the other. A recent finding the lab sheds light on this mechanism: the same proteins that trigger growth (cyclins) also repress initiation of meiosis. By measuring expression of specific meiotic regulators under conditions where cyclins are either absent or overexpressed, the mechanisms underlying repression of meiosis by cyclins will be defined (Specific Aim 1). The investigator has discovered the IME1 transcription is regulated like a 3-position switch; it is completely repressed under growth conditions, expressed to high levels under sporulation conditions, and expressed to moderate levels under conditions of carbon deprivation. The moderate level IME1 expression causes some cells to undergo recombination without chromosome segregation. This novel mechanism for transcriptional regulation, which involves interactions between several levels of control, will be dissected using a combination of yeast genetics and molecular biology (Specific Aim 2). Extracellular signals are generally considered to act at the beginning of a differentiation program, triggering a continuous progression of cellular changes. The investigator made the intriguing discovery that meiosis in yeast responds to extracellular signals at two distinct stages: prior to premeiotic DNA synthesis (early) and prior to chromosome segregation (late), and that the regulation at the two stages is different. To further examine this two-step control of differentiation, genes involved in nutritional control of late meiotic events are being identified, and their interactions with known meiotic regulators characterized (Specific Aim 3).

分化与增长之间的转换在 所有生物。 人类控制的丧失会导致癌症。 分化/增长开关通常由多个控制 细胞外信号，但分析了不同的关系 在大多数系统中，控制很困难。 一个简单的原型存在 二倍体酵母，其中三种不同类型的对照（细胞周期， 葡萄糖和乙酸盐相互作用，以调节生长与 减数分裂。酵母遗传学为分析这些提供了强大的工具 分别和组合的不同控制层。一个 增长/分化开关的主要特征是 程序是相互排斥的：单元格必须关闭一个程序 经历另一个。 最近发现实验室对此阐明了 机制：触发生长（细胞周期蛋白）的相同蛋白质也抑制 减数分裂的启动。 通过测量特定减数分裂的表达 在不存在或不存在细胞周期蛋白或 过表达的，通过抑制减数分裂的机制 细胞周期蛋白将被定义（特定目标1）。 调查员有 发现IME1转录的调节就像3位开关一样。 它在生长条件下完全被压抑，表示高 在孢子形成条件下的水平，并表达为中等水平 在碳剥夺条件下。 中等水平IME1 表达会导致某些细胞在没有染色体的情况下进行重组 隔离。 这种新颖的转录调节机制， 涉及几个控制层次之间的互动，将是 使用酵母遗传学和分子生物学的组合解剖 （特定目标2）。通常认为细胞外信号作用 在差异程序开始时，触发连续的 细胞变化的进展。 调查员让很有趣 发现酵母中的减数分裂对两个的细胞外信号反应 不同的阶段：前二氧化碳合成之前（早期）和之前 染色体分离（晚），并在两个阶段进行调节 是不同的。 进一步检查了这一两步控制 差异化，与减数分裂后期营养控制有关的基因 正在确定事件，并与已知减数分裂的互动 调节器的特征（特定目标3）。