Adenovirus interaction with cellular DNA repair responses (supplement)

腺病毒与细胞 DNA 修复反应的相互作用（补充）

基本信息

批准号：
9042684
负责人：
Eileen K BRIDGE
金额：
$ 5.83万
依托单位：
MIAMI UNIVERSITY OXFORD
依托单位国家：
美国
项目类别：
财政年份：
1999
资助国家：
美国
起止时间：
1999-09-30 至 2018-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9042684
关键词：
Adenovirus Infections Adenoviruses Apoptosis Binding Biological Assay Biological Models Cancer Biology Cell Communication Cell Cycle Cell Cycle Arrest Cell Cycle Checkpoint Cell Cycle Inhibition Cell Cycle Regulation Cell Nucleus Cell physiology Cells Characteristics Chromatin Chromosome abnormality Complex Concatenated DNA DNA DNA Damage DNA Repair DNA Tumor Viruses DNA biosynthesis DNA repair protein DNA-dependent protein kinase Defense Mechanisms Development Event Genome Genomic DNA Health Infection Ionizing radiation Lead Life Cycle Stages Ligation Malignant Neoplasms Measures Mediating Microscopy Mutation Nonhomologous DNA End Joining Nucleic Acids Phosphotransferases Process Protein Binding Proteins Protocols documentation Recruitment Activity Relative (related person)Repair Complex Replication Origin Role Training Viral Viral Genome Virus Virus Diseases Work ataxia telangiectasia mutated protein cancer cell gene therapy genetic regulatory protein genome integrity graduate student human CHEK1 protein insight mutant nuclease p53-binding protein 1 prevent repaired response sensor undergraduate student viral DNA

项目摘要

DESCRIPTION (provided by applicant): DNA repair mechanisms are essential for maintaining genome integrity following events that damage DNA. These responses are an important defense mechanism in stabilizing the genome and preventing mutations that can lead to cancer. DNA damage responses regulate the repair process itself, inhibit the cell cycle while repair takes place, and if the damage is severe, can induce cells to die by apoptosis. Viruses, including adenovirus, deliver their nucleic acid genomes to the cell, and this can sometimes lead to activation of cellular DNA damage responses. Our broad objectives are to understand how cellular DNA damage responses are 1) induced 2) coordinated to effect downstream processes of repair and cell cycle inhibition, and 3) able to regulate viral DNA replication. We expect our results to identify characteristics and activities of Ad genomes that are important for triggering different aspects of cellular DNA repair responses, and to provide insight into the mechanisms involved in coordinating the initial early DNA repair responses with activation of cellular protein that effect cell cycle inhibition, and "repair" adenovirus genomes by ligating them together to form concatemers. We will also study the ability of DNA damage proteins to interact with viral chromatin and assess the impact this has on viral DNA replication. This is relevant to a general understanding of the mechanisms involved in the initial activation of DNA repair responses, and how they are coordinated with activating downstream responses to maintain genome integrity and prevent the development of cancer cells. The proposed work is also relevant to the impact of DNA damage responses on other genome activities such as DNA replication. The fields encompassed by the project include cancer biology, virus host cell interactions, DNA damage responses, and DNA tumor viruses. The project will provide training for approximately 2 graduate students and 3-4 undergraduate students per year.

描述（由申请人提供）：DNA 修复机制对于在 DNA 损伤事件发生后维持基因组完整性至关重要。这些反应是稳定基因组和预防可能导致癌症的突变的重要防御机制。 DNA损伤反应调节修复过程本身，在修复发生时抑制细胞周期，如果损伤严重，可以诱导细胞凋亡。包括腺病毒在内的病毒将其核酸基因组传递至细胞，这有时会导致细胞 DNA 损伤反应的激活。我们的主要目标是了解细胞 DNA 损伤反应如何 1) 诱导 2) 协调以影响修复和细胞周期抑制的下游过程，以及 3) 能够调节病毒 DNA 复制。我们希望我们的结果能够确定 Ad 基因组的特征和活性，这些特征和活性对于触发细胞 DNA 修复反应的不同方面非常重要，并深入了解协调初始早期 DNA 修复反应与影响细胞周期的细胞蛋白激活所涉及的机制。抑制，并通过将腺病毒基因组连接在一起形成多联体来“修复”它们。我们还将研究 DNA 损伤蛋白与病毒染色质相互作用的能力，并评估其对病毒 DNA 复制的影响。这关系到对 DNA 修复反应初始激活机制的一般理解，以及它们如何与激活下游反应协调以维持基因组完整性并防止癌细胞的发展。拟议的工作还涉及 DNA 损伤反应对 DNA 复制等其他基因组活动的影响。该项目涵盖的领域包括癌症生物学、病毒宿主细胞相互作用、DNA损伤反应和DNA肿瘤病毒。该项目每年将为约2名研究生和3-4名本科生提供培训。