Meiotic Cdc7 Substrates and Regulation of NDT80 Transcription

减数分裂 Cdc7 底物和 NDT80 转录的调控

• 批准号: 7917074
• 负责人: Nancy M. Hollingsworth
• 金额: $ 34.43万
• 依托单位: STATE UNIVERSITY NEW YORK STONY BROOK
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-04-01 至 2015-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7917074
• 关键词: Affect; Alleles; Amino Acids; Behavior; Binding; Binding Sites; Biochemical; Biochemical Genetics; Biological Assay; CDC7 gene; Cell Count; Cell Cycle; Cell division; Cells; Chemicals; Chromosome Segregation; Chromosomes; Collaborations; Congenital Abnormality; DNA biosynthesis; Data; Diagnosis; Differentiation and Growth; Down Syndrome; Elements; Excision; Failure; Feedback; Fertilization; Gametogenesis; Gene Expression; Genes; Genetic Crossing Over; Genetic Transcription; Genomics; Germ Cells; Grant; Haploidy; In Vitro; Infertility; Kinetochores; Knowledge; Lead; Left; Malignant Neoplasms; Maps; Meiosis; Meiotic Recombination; Microtubules; Mitosis; Mitotic; Mitotic Cell Cycle; Modification; Molecular; Mono-S; Mutate; Organism; Phosphorylation; Phosphorylation Site; Phosphotransferases; Play; Prevention; Process; Proteins; Regulation; Replication Initiation; Repression; Reproduction; Reproduction spores; Role; Sister; Sister Chromatid; Site; System; Testing; Transcription factor genes; Transcriptional Activation; Work; Yeasts; analog; base; cohesin; cohesion; daughter cell; in vivo; insight; mutant; novel; novel strategies; promoter; transcription factor

Eukaryotic organisms utilize two types of cell division. Mitosis creates genetically identical daughter cells, thereby providing the raw material for growth and differentiation. Meiosis, in contrast, divides the chromosome number of cells in half, producing haploid gametes containing new combinations of alleles. This reduction is essential in keeping the chromosome number constant when two gametes fuse at fertilization. Mitosis and meiosis share many features in common: for example, chromosomes are segregated using microtubule based spindles, sister chromatids are held together by cohesins, and destruction of cohesins occurs via the same proteolytic machinery. Several meiosis-specific processes have evolved, however, to allow two divisions to occur after a single round of DNA replication such that homologous chromosomes, instead of sister chromatids, disjoin to opposite poles at Meiosis I. These include the connection of homologous chromosomes by a combination of crossing over and cohesion, the temporally distinct two step removal of cohesins at Meiosis I and Meiosis II and the mono-orientation of sister kinetochores at Meiosis I. Recent work has shown that these meiosis-specific processes result from the interplay between meiosis-specific proteins and mitotic cell cycle kinases such as CDK, Cdc5 and Cdc7. Using an analog sensitive conditional allele of CDC7, cdc7-as, my lab has shown that CDC7 is essential for meiotic recombination, mono-orientation of sister kinetochores and meiotic progression. The purpose of this grant is to use biochemical, genetic and genomic approaches to understand how Cdc7 regulates meiotic processes at the molecular level. In Aim 1, we will identify meiotic substrates of Cdc7 using novel strategies recently developed for use with analog sensitive kinases. In Aim 2, we will investigate how Cdc7 regulates the expression of NDTSO, a meiosis-specific transcription factor that acts a molecular switch to allow exit from pachytene, meiotic progression and differentiation of haploid products into spores.

真核生物利用两种类型的细胞分裂。有丝分裂产生基因完全相同的子细胞， 从而为生长和分化提供原料。相比之下，减数分裂将细胞分裂为两个细胞。 染色体数目减半，产生含有新的等位基因组合的单倍体配子。 当两个配子融合时，这种减少对于保持染色体数目恒定是必不可少的。 受精有丝分裂和减数分裂有许多共同的特征：例如， 使用基于微管的纺锤体进行分离，姐妹染色单体通过粘着蛋白结合在一起，并且 通过相同的蛋白水解机制破坏粘着蛋白。一些减数分裂特异性过程 然而，进化到允许在一轮DNA复制后发生两次分裂， 在减数分裂Ⅰ，同源染色体，而不是姐妹染色单体，分离成相反的两极。这些 包括同源染色体通过交换和凝聚的结合而连接， 在减数分裂I和减数分裂II时，时间上不同的两步去除粘连蛋白， 减数分裂I期的着丝粒。最近的研究表明，这些减数分裂特异性过程是由 减数分裂特异性蛋白和有丝分裂细胞周期激酶如CDK、Cdc 5和Cdc 7之间的相互作用。 利用CDC 7的一个类似物敏感的条件等位基因cdc 7-as，我们的实验室已经证明了CDC 7在减数分裂重组、姐妹着丝粒的单定向和减数分裂进程中是必不可少的。这项资助的目的是利用生物化学，遗传学和基因组学方法来了解Cdc 7如何在分子水平上调节减数分裂过程。在目的1中，我们将确定减数分裂底物Cdc 7使用新的策略，最近开发的类似物敏感的激酶。在目标2中，我们将研究Cdc 7如何调节NDTSO的表达，NDTSO是一种减数分裂特异性转录因子，其充当分子开关以允许从粗线期退出，减数分裂进展和单倍体产物分化为孢子。