REGULATION OF THE MEIOTIC CELL CYCLE

减数分裂细胞周期的调节

• 批准号: 7534524
• 负责人: ANGELIKA B AMON
• 金额: $ 23.78万
• 依托单位: MASSACHUSETTS INSTITUTE OF TECHNOLOGY
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-03-01 至 2009-12-14
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7534524
• 关键词: Biological; Cell Cycle; Cells; Centromere; Chromosome Arm; Chromosome Cohesion; Chromosome Segregation; Chromosomes; Congenital Abnormality; Cyclin-Dependent Kinases; DNA biosynthesis; Data; Development; Diagnostic; Drosophila polo protein; Event; Excision; Genes; Genetic Screening; Goals; Human; Kinetochores; Meiosis; Mitosis; Mitotic; Mitotic Cell Cycle; Molecular; Molecular Genetics; Pattern; Phase; Phosphoric Monoester Hydrolases; Process; Protein phosphatase; Proteins; Regulation; Research Personnel; Role; Saccharomyces cerevisiae; Sister Chromatid; Spontaneous abortion; Techniques; Testing; Therapeutic; cohesion; gene function; prevent; programs; protector protein; segregation

During the mitotic cell cycle a single round of DNA replication is followed by a chromosome segregation phase. Meiosis is a specialized cell cycle in which a single DNA replication phase is followed by two consecutive chromosome segregation phases. During the first meiotic division (meiosis I), homologous chromosomes are segregated whereas during the second meiotic division (meiosis II) sister chromatids are divided. Meiosis-specific regulators of chromosome segregation are likely to act on the machinery common to mitotic and meiotic chromosome segregation, to bring about the meiotic chromosome segregation program. We propose to study two aspects of this unusual cell cycle. First, we will examine the transition between the first and the second meiotic division, during which conditions are established that facilitate a second round of chromosome segregation rather than DNA replication. Second, we will examine how the unusual meiosis I chromosome segregation pattern is established. To determine howthe meiosis I - meiosis II transition is controlled we will characterize the function of the protein phosphatase Cdc14, which has been shown to control the analogous transition, the mitosis - G1 transition during the mitotic cell cycle. We will assess howCdc14 controls the meiosis I - meiosis II transition anddetermine howCdc14 is itself regulated during meiosis. Two approaches will be taken to characterize the events necessary to establish the meiosis I chromosome segregation pattern. (1) We will determine how Spo13, a protein known to regulate meiotic chromosome segregation, regulates this process. (2) We will characterize the role of genes we recently identified through a genetic screen, in establishing the meiosis I chromosome segregation. Chromosome mis-segregation during meiosis is a leading cause of birth defects and the leading cause of miscarriages in humans. It is, therefore, vital to understand the molecular mechanisms that regulate the meiotic cell cycle to open avenues towards the development of diagnostics and therapeutics.

在有丝分裂细胞周期中，单轮DNA复制之后是染色体分离 相位减数分裂是一个特殊的细胞周期，其中单个DNA复制阶段之后是两个 连续的染色体分离阶段。在第一次减数分裂（减数分裂I）期间，同源 染色体分离，而在第二次减数分裂（减数分裂II）期间，姐妹染色单体分离。 divided.染色体分离的减数分裂特异性调节剂可能作用于共同的机制， 有丝分裂和减数分裂染色体分离，导致减数分裂染色体分离 程序.我们建议研究这种不寻常的细胞周期的两个方面。首先，我们将研究 在第一次和第二次减数分裂之间，在此期间建立了促进减数分裂的条件。 第二轮染色体分离而不是DNA复制。第二，我们将研究 建立了不寻常的减数分裂I染色体分离模式。为了确定减数分裂I -减数分裂 II转换是受控的，我们将描述蛋白磷酸酶Cdc 14的功能，它已经被 显示控制类似的过渡，有丝分裂细胞周期中的有丝分裂- G1过渡。我们将 评估Cdc 14如何控制减数分裂I -减数分裂II的转换，并确定Cdc 14本身是如何调节的。 在减数分裂期间。将采取两种方法来表征建立减数分裂I所必需的事件 染色体分离模式(1)我们将确定Spo 13，一种已知调节减数分裂的蛋白质 染色体分离，调节这一过程。(2)我们将描述基因的作用，我们最近 通过遗传筛选鉴定，在建立减数分裂I染色体分离。 减数分裂期间的染色体错误分离是出生缺陷的主要原因，也是导致新生儿死亡的主要原因。 人类的流产因此，了解调节细胞凋亡的分子机制是至关重要的。 减数分裂细胞周期的研究，为诊断和治疗的发展开辟了道路。