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: 6386969
• 负责人: SAUL M HONIGBERG
• 金额: $ 16.24万
• 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/6386969
• 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是精确调节的， 所有的有机体。 人类失去这种控制可能导致癌症。 分化/增长开关通常由多个 细胞外信号，但分析不同之间的关系 控制在大多数系统中是困难的。 一个简单的原型存在于 二倍体酵母，其中三种不同类型的对照（细胞周期， 葡萄糖和乙酸盐相互作用，调节生长和生长之间的转换。 减数分裂酵母遗传学提供了一个强大的工具来分析这些 不同的控制层，无论是单独还是组合。一 生长/分化开关的中心特征是， 程序是相互排斥的：细胞必须关闭一个程序， 接受另一个。 该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）也抑制 减数分裂的开始。 通过测量特定减数分裂的表达， 调节剂的条件下，细胞周期蛋白要么不存在， 过表达，减数分裂的抑制机制， 将定义细胞周期蛋白（具体目标1）。 研究者已 发现IME 1转录像3位开关一样被调节; 它在生长条件下被完全抑制，表达至高水平， 孢子形成条件下的水平，并表达至中等水平 在碳剥夺的条件下。 中等水平的IME 1 表达导致一些细胞经历没有染色体的重组， 隔离。 这种新的转录调控机制， 涉及到几个控制层次之间的相互作用，将是 结合酵母遗传学和分子生物学 （具体目标2）。细胞外信号通常被认为是 在分化程序开始时，触发连续的 细胞变化的进展。 调查员做了一个有趣的 发现酵母的减数分裂对细胞外信号有反应， 不同的阶段：减数分裂前DNA合成（早期）和减数分裂前 染色体分离（晚期），并在这两个阶段的调控 不一样. 为了进一步研究这种两步控制， 减数分裂后期营养调控基因 事件正在确定，它们与已知的减数分裂的相互作用 监管机构的特点（具体目标3）。