Cell Progression Through Meiosis: A Signal From Recombination to the First Division

减数分裂是一个高度保守的特殊的细胞分裂过程，在这个过程中产生配子。 在染色体水平，“减数分裂前”DNA合成、重组和联会、减数分裂、均等分裂和包装（进入精子、孢子等）所有这些都必须协调一致，并按正确的顺序和时间进行。本研究的长期目标是了解减数分裂中的染色体行为，本项目的重点是了解减数分裂中独特且必不可少的两个步骤之间的通信：重组和第一次（MI）减数分裂染色体分裂。利用酵母S.研究人员在研究酿酒酵母时，定义了正常细胞减数分裂中的一种通讯模式;他将其称为“重组起始信号”（RIS），因为它需要启动重组的基因产物。在野生型（WT）细胞中RIS的正常结果是延迟MI分裂，以便有时间进行重组;缺乏信号的突变体开始MI分裂较早。在目前的NSF资助期间，研究人员已经表明，减数分裂RIS需要重组起始基因REC 102，REC 104，MER 2/REC 107，REC 114，SPO 11和RAD 50（但不是MEI 4或REC 103/SKI 8）以及联会复合体基因HOP 1和RED 1。RIS不是传统的阻止突变/缺陷细胞的检查点：WT细胞具有延迟。在资助的一年里，实验室将重点关注两个领域。首先，他们将研究RIS如何被转导以延迟MI分裂的机制。他们发现有丝分裂DNA损伤检查点（尽管对晚期重组检查点很重要）不参与RIS的转导。他们将测试另外两个研究得很好的检查点，DNA合成检查点和纺锤体检查点，以确定它们是否在RIS中起作用。研究的第二个目的是确定RIS（减数分裂转录激活因子NDT 80）的靶标如何受到影响。他们已经证明，在不存在RIS的情况下，NDT 80转录增加，并且在更早的时间产生活性蛋白。为了理解WT细胞中发生的正常RIS延迟的机制，他们将检查该调节器的上游调节器和翻译后修饰剂，以确定它们中的哪一个响应RIS。这两种方法的结合将有助于确定重组是如何与减数分裂过程中的减数分裂协调。调查员积极参与教学本科生和研究生都必要的批判性思维设计实验，以促进我们对自然生物过程的理解和技术，以实现它们。 通过这个项目，研究人员应该产生有价值的科学见解和深思熟虑，训练有素的研究人员。

Meiosis is the highly conserved, special cell division process in which gametes are made. At the chromosome level, "premeiotic" DNA synthesis, recombination and synapsis, the reductional division, the equational division, and packaging (into sperm, spores, etc.) all must be coordinated and occur in the right order and time. The long-range goal of this research is the understanding of chromosome behavior in meiosis and the focus of this project is the understanding of the communication between two steps unique to, and essential for, meiosis: recombination and the first (MI) meiotic chromosome division. Using the yeast S. cerevisiae, the investigator has defined a mode of communication in meiosis that occurs in normal cells; he refers to this as the "recombination initiation signal" (RIS) because it requires gene products that initiate recombination. The normal outcome of the RIS in wild type (WT) cells is to delay the MI division to allow time for recombination to proceed; mutants lacking the signal begin the MI division at an earlier time. During the current NSF grant, the investigator has shown that the meiotic RIS requires the recombination initiation genes REC102, REC104, MER2/REC107, REC114, SPO11, and RAD50 (but not MEI4 or REC103/SKI8) and the synaptonemal complex genes HOP1 and RED1. The RIS is not a traditional checkpoint that arrests mutant/defective cells: it is WT cells that have the delay. During the year of funding the laboratory will focus on two areas. First they will examine the mechanism of how the RIS is transduced to delay the MI division. They have discovered that the mitotic DNA damage checkpoint (although important for a late recombination checkpoint) is not involved in transducing the RIS. They will test two other well-studied checkpoints, the DNA synthesis checkpoint and the spindle checkpoint, to determine if they have a role in the RIS. The second aim of the research is to determine how the target of the RIS (the meiotic transcriptional activator NDT80) is affected. They have demonstrated that NDT80 transcription is increased and active protein is produced at earlier times in the absence of the RIS. To understand the mechanism of the normal RIS delay which occurs in WT cells, they will examine the upstream regulators and posttranslational modifiers of this regulator to determine which of them respond to the RIS. The combination of these two approaches will help to define how recombination is coordinated with the reductional division during meiosis.The investigator is actively involved in teaching undergraduate and graduate students both the critical thinking necessary to design experiments to advance our understanding of natural biological processes and the techniques to carry them out. Through this project the investigator should produce valuable scientific insights and thoughtful, well-trained researchers.