MECHANISM(S) CONTROLLING GROWTH/MEIOSIS SWITCH IN YEAST

分化和生长之间的切换受到精确的调控 所有的有机体。人类失去这种控制可能会导致癌症。 分化/增长开关通常由多个 细胞外信号，但分析不同信号之间的关系 在大多数系统中，控制是困难的。一个简单的原型存在于 二倍体酵母，其中三种不同类型的控制(细胞周期， 葡萄糖和醋酸盐相互作用，调节生长和生长之间的切换 减数分裂。酵母遗传学为分析这些基因提供了强有力的工具。 不同的控制层，包括单独控制和组合控制。一个 增长/分化开关的主要特征是，这两个 程序是相互排斥的：单元必须关闭一个程序才能 经历另一种。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 开始减数分裂。通过测量特定减数分裂的表达 在没有周期蛋白或没有周期蛋白的情况下的监管机构 过度表达，抑制减数分裂的机制 将定义周期药物(具体目标1)。调查员已经 发现IME1的转录调控像一个3位开关； 它在生长条件下完全被抑制，表现为高 在产孢子条件下的水平，并表达到中等水平 在碳匮乏的条件下。中等水平的IME1 表达导致一些细胞发生重组，而不是染色体 种族隔离。这一转录调控的新机制， 涉及几个控制级别之间的交互，将是 结合酵母遗传学和分子生物学进行解剖 (具体目标2)。细胞外信号通常被认为是作用于 在差异化计划开始时，触发连续的 细胞变化的进展。调查员做出了耐人寻味的 酵母减数分裂对胞外信号的反应 不同的阶段：减数分裂前DNA合成之前(早期)和之前 染色体分离(晚期)，以及两个阶段的调节 是不同的。为了进一步研究这种两步控制 分化，参与减数分裂后期营养控制的基因 正在确定事件及其与已知的减数分裂的相互作用 监管者的特征(具体目标3)。

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).