REGULATION OF THE MEIOTIC CELL CYCLE

描述（由申请人提供）：在有丝分裂细胞周期中，一轮DNA复制之后是染色体分离阶段。减数分裂是一个特殊的细胞周期，其中一个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，姐妹染色单体分裂。染色体分离的减数分裂特异性调节因子可能作用于有丝分裂和减数分裂染色体分离的共同机制，从而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，我们将研究第一次和第二次减数分裂之间的过渡，在此期间建立了促进第二轮染色体分离而不是DNA复制的条件。其次，我们将研究不寻常的减数分裂I染色体分离模式是如何建立的。为了确定如何控制减数分裂I -减数分裂II过渡，我们将描述蛋白磷酸酶Cdc14的功能，该酶已被证明在有丝分裂细胞周期中控制类似的过渡，即有丝分裂- G1过渡。我们将评估Cdc14如何控制减数分裂I -减数分裂II的转变，并确定Cdc14在减数分裂过程中如何调节自身。将采取两种方法来描述建立减数分裂I染色体分离模式所必需的事件。(1)我们将确定Spo13（一种已知调节减数分裂染色体分离的蛋白质）如何调节这一过程。(2)我们将描述我们最近通过遗传筛选鉴定的基因在建立减数分裂I染色体分离中的作用。在减数分裂期间染色体错误分离是导致出生缺陷和人类流产的主要原因。因此，了解调节减数分裂细胞周期的分子机制对于开发诊断和治疗方法至关重要。

DESCRIPTION (provided by applicant): 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 how the 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 how Cdc14 controls the meiosis I - meiosis II transition and determine how Cdc14 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.