A novel function of Orc6 during mitosis in S. cerevisiae

Orc6 在酿酒酵母有丝分裂过程中的新功能

• 批准号: 7852515
• 负责人: Amy E Ikui
• 金额: $ 15.7万
• 依托单位: BROOKLYN COLLEGE
• 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 2013-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7852515
• 关键词: Affect; Autonomous Replication; Binding; Cancer cell line; Categories; Cell Cycle; Cell Cycle Progression; Cell Cycle Stage; Cell division; Cells; Centromere; Characteristics; Chromosomal Instability; Chromosome Segregation; Chromosomes; Complex; Cyclins; DNA; DNA biosynthesis; Defect; Ensure; Eukaryota; Eukaryotic Cell; Event; Flow Cytometry; Funding; Future; Generations; Genes; Genetic; Genome; Genomics; Goals; Human; Kinetochores; Lead; Malignant Neoplasms; Microarray Analysis; Mitosis; Mitotic; Molecular; Mutagenesis; Mutation; Nocodazole; Paper; Peer Review; Phase; Play; Process; Protein Subunits; Proteins; Publications; Replication Initiation; Research; Role; Saccharomyces cerevisiae; Screening procedure; Sister Chromatid; Structure; Students; Suppressor Genes; System; Temperature; Testing; Work; Yeasts; career; chromosome loss; cohesin; cohesion; college; daughter cell; design; genetic analysis; genome-wide; hydroxyurea; innovation; mutant; novel; origin recognition complex; protein complex; protein function; research study; segregation; success; temperature sensitive mutant; tumorigenesis

DESCRIPTION (provided by applicant): Eukaryotic cells duplicate their chromosomes during S-phase, and segregate the chromosomes into two daughter cells during mitosis. Errors in the chromosome segregation could lead to gain or loss of chromosome. This is a cause of chromosome instability which is a hallmark of tumorigenesis. Our long-term goal is to understand the molecular mechanism of accurate chromosome segregation in S. cerevisiae. Orc6p controls DNA replication from yeast to humans. Recently it has been proposed that Orc proteins might also have mitotic functions besides its well characterized function in DNA replication. Human Orc6p is localized to kinetochore, and has been implicated in the control of chromosome segregation. However it is not clear how Orc6p controls mitosis. I hypothesize that Orc6p has a mitotic function in S. cerevisiae. To study the mitotic function of Orc6p in S. cerevisiae; (1) a conditional mutant of orc6 will be isolated and characterized. (2) Protein localization will be analyzed to see if Orc6p is localized kinetochore during mitosis. (3) A suppressor gene screening using the orc6 conditional mutant will be conducted to reveal the specific genetic interactions between ORC6 and mitotic genes. Successful isolation of orc6 mutant which is defective only during mitosis will help us to study the mitotic function of Orc6p. Kinetochore localization of Orc6p will ensure that Orc6p has a role in chromosome segregation. Suppressor gene screening will help us to understand the molecular mechanism of Orc6 function. Orc6p is conserved from yeast to humans. The results obtained from this study can be applied to understand the molecular function of Orc6p in higher eukaryotes. The accurate chromosome segregation is a critical step during mitosis to avoid chromosome instability. It is important to study the mechanism of chromosome segregation in eukaryotes to understand the molecular mechanism of tumorigenesis.

描述（由申请人提供）：真核细胞在S期间复制其染色体，并在有丝分裂期间将染色体隔离为两个子细胞。染色体分离的错误可能导致染色体的增益或损失。这是染色体不稳定性的原因，这是肿瘤发生的标志。我们的长期目标是了解酿酒酵母中准确的染色体分离的分子机制。 ORC6P控制着从酵母到人类的DNA复制。最近，有人提出，除了其在DNA复制中的特征功能外，ORC蛋白还具有有丝分裂功能。人ORC6P局部定位于动力学，并与染色体分离的控制有关。但是，尚不清楚ORC6P如何控制有丝分裂。我假设ORC6P在酿酒酵母中具有有丝分裂功能。研究ORC6P在酿酒酵母中的有丝分裂功能； （1）将分离和表征ORC6的条件突变体。 （2）将分析蛋白质定位，以查看ORC6P在有丝分裂过程中是否是局部的动力学。 （3）将进行使用ORC6条件突变体进行抑制基因筛选，以揭示ORC6与有丝分裂基因之间的特定遗传相互作用。仅在有丝分裂期间有缺陷的ORC6突变体的成功分离将有助于我们研究ORC6P的有丝分裂功能。 ORC6P的动力学定位将确保ORC6P在染色体分离中起作用。抑制基因筛选将有助于我们了解ORC6功能的分子机制。 ORC6P从酵母到人都保存。从这项研究中获得的结果可用于了解较高真核生物中ORC6P的分子功能。准确的染色体分离是有丝分裂过程中避免染色体不稳定性的关键步骤。重要的是研究真核生物中染色体分离的机制，以了解肿瘤发生的分子机制。