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).

分化和生长之间的转换受到精确调节 所有生物体。 人类失去这种控制可能会导致癌症。 分化/生长开关通常由多个控制 细胞外信号，但分析不同信号之间的关系 在大多数系统中控制是很困难的。 一个简单的原型存在于 二倍体酵母，其中三种不同类型的控制（细胞周期， 葡萄糖和醋酸盐相互作用来调节生长和生长之间的转换 减数分裂。酵母遗传学为分析这些提供了强大的工具 不同层次的控制可以单独进行，也可以组合进行。一个 生长/分化开关的中心特征是两个 程序是相互排斥的：细胞必须关闭一个程序才能 经历另一个。 实验室最近的一项发现揭示了这一点 机制：触发生长的相同蛋白质（细胞周期蛋白）也会抑制 减数分裂的开始。 通过测量特定减数分裂的表达 在细胞周期蛋白不存在或不存在的条件下调节 过度表达，减数分裂抑制机制 将定义细胞周期蛋白（具体目标 1）。 调查员有 发现 IME1 转录像 3 位开关一样受到调节； 它在生长条件下被完全抑制，表达到高 孢子条件下的水平，并表示为中等水平 在碳匮乏的条件下。 中等级别 IME1 表达导致一些细胞在没有染色体的情况下进行重组 隔离。 这种转录调控的新机制 涉及多个控制级别之间的相互作用，将是 结合酵母遗传学和分子生物学进行剖析 （具体目标 2）。通常认为细胞外信号起作用 在分化计划开始时，触发连续 细胞变化的进展。 调查员做出了耐人寻味的事 发现酵母减数分裂对细胞外信号作出反应 不同阶段：减数分裂前 DNA 合成之前（早期）和之前 染色体分离（晚期），以及两个阶段的调控 是不同的。 为了进一步检验这种两步控制 分化，参与减数分裂晚期营养控制的基因 事件正在被识别，以及它们与已知的减数分裂的相互作用 监管机构的特征（具体目标 3）。