The Coordination of Recombination Initiation and the First Division in Meiosis

减数分裂是一种高度保守的、特殊的细胞分裂过程，在这个过程中，真核生物产生配子。减数分裂染色体事件、减数分裂前DNA合成、重组和突触、第一次还原分裂、第二次等速分裂和包装（成精子、卵子、孢子等）都必须协调一致，并在正确的顺序和时间内发生。Malone博士的长期目标是了解染色体在减数分裂中的行为，而这个项目的目标是明确了解减数分裂中两个独特且必不可少的步骤之间的协调：重组和第一次减数分裂染色体分裂。本研究探讨了在重组开始时所涉及的功能调节随后染色体分离的可能性。在酿酒酵母（和其他生物）中，协调这两个步骤的两种方法是众所周知的：重组检查点监测遗传重组的后期阶段，纺锤体检查点监测纺锤体-着丝点附着和染色体张力（重组有助于）。该研究人员发现了另一种协调模式的证据，涉及启动重组所需的基因产物子集的存在，证据表明野生型细胞识别这些基因产物的存在，并通过延迟第一次分裂所需的调节因子（NDT80）的表达来做出反应。Malone博士假设这八种起始功能需要形成一个信号来调节NDT80的表达和分裂。他通过提出以下三个问题来验证这一假设：1)起始蛋白是否与它们对第一条染色体分离时间的影响相一致的模式相互作用；2)所提出的途径是否真的与纺锤体检查点可分离，已知纺锤体检查点参与识别未重组的染色体；3)细胞如何感知起始蛋白的存在并调节NDT80的表达？这项研究将揭示染色体（遗传信息）在“高级细胞”中产生生殖细胞（如精子和卵子）的过程（减数分裂）中是如何表现的。这一过程对于所有高等细胞和大多数非细菌细胞的世代改变是绝对必要的。研究者有数据表明，只有在减数分裂期间发生的两个特殊事件是共同调节的。本文提出的工作验证了这一假设。由于减数分裂是所有高等细胞遗传学的基础，因此了解减数分裂的机制是真正理解遗传学的核心。因此，这里的研究不仅解决了基本的生物学机制，而且产生了适用于主要科学方法-遗传学的信息。除了对生命系统的基本知识作出贡献外，这项研究还将培训新的年轻科学家，包括研究生和本科生；这对国家保持其在世界科学界的地位至关重要。此外，这笔资金将允许实验室在学年和夏季参与少数民族学生的科学培训。

Meiosis is the highly conserved, special cell division process in which gametes are made in eukaryotes. Meiotic chromosome events, premeiotic DNA synthesis, recombination and synapsis, the first reductional division, the second equational division, and packaging (into sperm, eggs, spores, etc.) all must be coordinated and occur in the right order and time. Dr. Malone's long range goal is to understand chromosome behavior in meiosis, and the goal of this project is specifically to understand the coordination between two steps unique to, and essential for, meiosis: recombination and the first meiotic chromosome division. This research explores the possibility that functions involved at the start of recombination modulate the subsequent separation of chromosomes. In the yeast S. cerevisiae (and other organisms), two methods of coordinating these two steps are well known: the recombination checkpoint monitoring later stages of genetic recombination, and the spindle checkpoint, monitoring spindle-kinetochore attachment and chromosome tension (to which recombination contributes). This investigator has found evidence for another mode of coordination involving the presence of a subset of the gene products required to initiate recombination, evidence that wild type cells recognize the presence of these gene products and respond by delaying the expression of a regulator (NDT80) required for the first division. Dr. Malone hypothesizes that the eight initiation functions required form a signal that modulates NDT80 expression and hence division. He tests this hypothesis by asking the following three questions: 1) Do initiation proteins interact with patterns consistent with their effects on the timing of first chromosome separation; 2) Is the proposed pathway truly separable from the spindle checkpoint, known to be involved in recognizing unrecombined chromosomes; and 3) How do cells sense the presence of the initiation proteins and modulate NDT80 expression?This research will shed light on how chromosomes (the genetic information) behave when they go through the process (meiosis) that leads, in "higher cells", to the generation of sex cells such as sperm and eggs. This process is absolutely required for the alteration of generations of all higher cells, and the majority of nonbacterial cells. The investigator has data indicating that two special events that only happen during meiosis are coregulated. The work presented here tests this hypothesis. Since meiosis is the basis of genetics for all higher cells, understanding of the mechanism of meiosis is central to truly understanding genetics. Thus the research here not only addresses a basic biological mechanism, but it generates information applying to a major scientific approach--genetics. In addition to the contribution to basic knowledge of living systems, the research will allow the training of new young scientists, both as graduate students and as undergraduates; this is critical for the nation to maintain its position in the world of science. In addition, the funding will allow the laboratory to participate in the scientific training of minority students during both the school year and the summer.