权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

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

基本信息

批准号：
8241917
负责人：
Amy E Ikui
金额：
$ 15.54万
依托单位：
BROOKLYN COLLEGE
依托单位国家：
美国
项目类别：
财政年份：
2010
资助国家：
美国
起止时间：
2010-04-01 至 2013-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8241917
关键词：
Affect Autonomous Replication Binding Cancer cell line Categories Cell Cycle Cell Cycle Progression Cell Cycle Stage Cell division Cells Centromere ChIP-on-chip 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 Play Process Protein Subunits Proteins Publications Replication Initiation Research Role S Phase Saccharomyces cerevisiae Screening procedure Sister Chromatid Structure Suppressor Genes System Temperature Testing Work Yeasts career chromosome loss cohesin cohesion college daughter cell design genetic analysis genome-wide graduate student hydroxyurea innovation mutant novel origin recognition complex protein complex protein function research study segregation success temperature sensitive mutant tumorigenesis undergraduate student

项目摘要

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(申请人提供)：真核细胞在S期复制染色体，有丝分裂时将染色体分离成两个子细胞。染色体分离的错误会导致染色体的获得或丢失。这是染色体不稳定的原因之一，而染色体不稳定是肿瘤发生的标志。我们的长期目标是了解酿酒酵母染色体准确分离的分子机制。Orc6p控制从酵母到人类的DNA复制。最近有人提出，ORC蛋白除了在DNA复制中具有特有的功能外，还可能具有有丝分裂功能。人类Orc6p定位于着丝粒，并参与了染色体分离的控制。然而，目前还不清楚Orc6p是如何控制有丝分裂的。我推测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)分离并鉴定ORC6的条件突变体。(2)分析Orc6p在有丝分裂过程中的定位，以确定Orc6p是否是定位的动粒。(3)利用ORC6条件突变体进行抑癌基因筛选，以揭示ORC6与有丝分裂基因之间的特异性遗传相互作用。成功分离到只在有丝分裂过程中有缺陷的ORC6突变体，将有助于我们研究Orc6p的有丝分裂功能。Orc6p的动粒定位将确保Orc6p在染色体分离中发挥作用。抑癌基因的筛选将有助于我们了解ORC6功能的分子机制。Orc6p从酵母到人类都是保守的。本研究结果可用于了解Orc6p在高等真核生物中的分子功能。准确的染色体分离是有丝分裂过程中避免染色体不稳定的关键步骤。研究真核生物中染色体分离的机制对于理解肿瘤发生的分子机制具有重要意义。