The Coordination of Recombination Initiation and the First Division in Meiosis

减数分裂是在真核生物中形成配子的高度保守的特殊细胞分裂过程。减数分裂染色体事件，减数分裂前DNA合成，重组和联会，第一次还原分裂，第二次方程分裂，以及包装(进入精子、卵子、孢子等)。所有这些都必须协调一致，并以正确的顺序和时间发生。马龙博士的长期目标是了解减数分裂中的染色体行为，而这个项目的目标是明确了解减数分裂特有且必不可少的两个步骤之间的协调：重组和第一次减数分裂染色体分裂。这项研究探索了重组开始时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，两种协调这两个步骤的方法是众所周知的：重组检查点监测基因重组的后期阶段，纺锤体检查点监测纺锤体-动粒连接和染色体张力(重组对此有贡献)。这位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的子集的存在，证据表明野生型细胞识别这些基因产物的存在，并通过推迟第一次分裂所需的调控因子(NDT80)的表达来做出反应。马龙博士假设，所需的八个启动功能形成了一个信号，该信号调节NDT80的表达，从而调节分裂。他通过提出以下三个问题来验证这一假设：1)启动蛋白是否与它们对首次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可以从纺锤体检查点分离出来，已知这涉及识别未重组的染色体；以及3)细胞如何感知启动蛋白的存在并调节NDT80的表达？这项研究将揭示染色体(遗传信息)在“高等细胞”中导致精子和卵子等性细胞产生的过程(减数分裂)时的表现。这一过程对于所有高等细胞和大多数非细菌细胞的世代变化是绝对必要的。研究人员有数据表明，只发生在减数分裂期间的两个特殊事件是共同调节的。这里提出的工作验证了这一假说。由于减数分裂是所有高等细胞的遗传学基础，了解减数分裂的机制是真正理解遗传学的核心。因此，这里的研究不仅涉及基本的生物学机制，而且产生了应用于主要科学方法--遗传学--的信息。除了对生命系统基本知识的贡献外，这项研究还将培养新的年轻科学家，无论是研究生还是本科生；这对国家保持其在科学界的地位至关重要。此外，这笔资金将使该实验室能够在学年和暑假期间参与对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.