Chromosome Inheritance

染色体遗传

• 批准号: 7225414
• 负责人: BRUCE W. STILLMAN
• 金额: $ 63.88万
• 依托单位: COLD SPRING HARBOR LABORATORY
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-01-01 至 2011-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7225414
• 关键词: Address; Adenoviruses; Affect; Binding; Binding Proteins; Biochemical; Biology; Cell Cycle; Cell division; Cell physiology; Cells; Centrioles; Centromere; Centrosome; Chromatin Modeling; Chromosome Segregation; Chromosomes; Collaborations; Complex; Cytokinesis; DNA Tumor Viruses; DNA biosynthesis; DNA replication origin; Disruption; Eukaryotic Cell; Event; Funding; Genes; Genetic; Genetic Screening; Genome; Genomics; Goals; Grant; Hematopoietic stem cells; Heterochromatin; Human; Human Herpesvirus 4; Inheritance Patterns; Interphase Cell; Kinetochores; Learning; Libraries; Link; Localized; Maintenance; Malignant Neoplasms; Mediating; Methods; Microtubule-Organizing Center; Mitosis; Modification; Mus; National Institute of General Medical Sciences; Nature; Normal Cell; Phase; Plasmids; Pre-Replication Complex; Process; Proteins; Proteomics; RNA Interference; Regulatory Pathway; Replication Initiation; Research; Research Support; Role; Signal Transduction; Simian virus 40; Source; Staging; Time; Ubiquitin; Virus; Virus Replication; Yeasts; anticancer research; base; cancer cell; chromatin assembly factor I; chromosome replication; in vivo; interest; neoplastic cell; novel; origin recognition complex; programs; reconstitution

Understanding the mechanism of inheritance of chromosomes in human cells is a fundamental problem in biology and has direct relevance to cancer research. Alterations to the normal pattern of inheritance promote progression to cancer by the accumulation of somatic genetic aberrations in the genome of tumor cells. The regulatory pathways investigated by others in this Program Project directly control the DNA replication and mitosis. The proposed studies focus how a cell duplicates and segregates chromosomes and are based on the observation that Origin Recognition Complex (ORC) in human cells participates in many of these processes. ORC is required for the initiation of DNA replication and recent research has demonstrated that ORC, or ORC subunits participate in other aspects of chromosome inheritance and cell division. The first aim will address the dynamic assembly of ORC during the cell division cycle and determine how this process is regulated. A second aim will identify and characterize ORC associated proteins in chromosome inheritance, suing both proteomic methods (with Core D) and genetic approaches with an RNAi library (Core B) to discover cellular proteins essential for Epstein Barr Virus replication. A third aim will expand research on the role of ORC in maintenance of heterochromatin and a potential relationship with the RNAi machinery maintaining heterochromatin. A final aim will study the role of ORC subunits in centrosomes duplication and control chromosome segregation. Although the cell division cycle regulatory machinery coordinates the multiple stages of the chromosome inheritance cycle, research in this Project suggests a more fundamental connection between the actual processes of DNA replication and chromosome segregation. Thus these studies on chromosome inheritance are directly relevant to the overall goals of the program project and the other projects in the Program.

了解人类细胞染色体的遗传机制是人类细胞中的一个基本问题。 生物学，与癌症研究有直接关系。正常继承模式的改变 通过肿瘤基因组中体细胞遗传畸变的积累促进癌症的进展 细胞。本项目中其他人研究的调控途径直接控制 DNA 复制和有丝分裂。拟议的研究重点是细胞如何复制和分离染色体以及 基于人类细胞中的起源识别复合体（ORC）参与许多 这些过程。 ORC 是 DNA 复制启动所必需的，最近的研究表明 ORC或ORC亚基参与染色体遗传和细胞分裂的其他方面。这 第一个目标是解决细胞分裂周期中 ORC 的动态组装问题，并确定其如何进行 过程受到监管。第二个目标是鉴定和表征染色体中的 ORC 相关蛋白 继承，使用蛋白质组学方法（Core D）和使用 RNAi 文库的遗传方法（Core D） B) 发现 Epstein Barr 病毒复制所必需的细胞蛋白。第三个目标是扩大研究范围 ORC 在异染色质维持中的作用及其与 RNAi 机制的潜在关系 维持异染色质。最终目标是研究 ORC 亚基在中心体复制和 控制染色体分离。尽管细胞分裂周期调节机制协调 染色体遗传周期的多个阶段，该项目的研究提出了一个更基本的 DNA复制和染色体分离的实际过程之间的联系。因此这些 染色体遗传研究直接关系到该计划项目的总体目标和 该计划中的其他项目。