The Coordination of Recombination Initiation and the First Division in Meiosis

重组起始与减数分裂第一次分裂的协调

• 批准号: 0743983
• 负责人: Robert Malone
• 金额: $ 45万
• 依托单位: University of Iowa
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-07-01 至 2012-06-30
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=0743983&HistoricalAwards=false
• 关键词: Coordination; Recombination; Initiation; First; Division

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.

减数分裂是真核生物产生配子的一个高度保守、特殊的细胞分裂过程。 减数分裂染色体事件，减数分裂前DNA合成，重组和联会，第一次减数分裂，第二次减数分裂和包装（进入精子，卵子，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。马龙博士的长期目标是了解减数分裂中的染色体行为，本项目的目标是特别了解减数分裂中独特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。这项研究探讨了重组开始时所涉及的功能调节随后染色体分离的可能性。在酵母S.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，以及纺锤体检查点，监测纺锤体-动粒附着和染色体张力（重组对其有贡献）。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的子集的存在，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（NDT 80）的表达来响应的证据。马龙博士假设，这八种起始功能需要形成一个信号，调节NDT 80的表达，从而分裂。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次染色体分离时间的影响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分离，已知纺锤体检查点参与识别未结合的染色体; 3）细胞如何感知起始蛋白的存在并调节NDT 80表达？这项研究将揭示染色体（遗传信息）在经历导致“高等细胞”产生精子和卵子等性细胞的过程（减数分裂）时的行为。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。研究人员的数据表明，仅在减数分裂期间发生的两个特殊事件是共同调节的。本文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对于真正理解遗传学至关重要。因此，这里的研究不仅解决了一个基本的生物机制，但它产生的信息适用于一个主要的科学方法-遗传学。 除了对生命系统的基本知识做出贡献外，这项研究还将培养新的年轻科学家，包括研究生和本科生;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夏季参加少数民族学生的科学培训。