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修复机制对于在损害DNA的事件之后保持基因组完整性至关重要。这些反应是稳定基因组并防止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，在进行修复时抑制细胞周期，如果损伤严重，可以诱导细胞死亡。包括腺病毒在内的病毒将其核酸基因组传递到细胞，这有时会导致细胞DNA损伤反应的激活。我们的广泛目标是了解细胞DNA损伤反应是如何的1）诱导的2）协调以实现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基因组的特征和活动，这些特征和活动对于触发细胞DNA修复反应的不同方面至关重要，并提供对协调初始早期DNA修复反应的机制，从而激活细胞周期抑制细胞蛋白，以及“修复”腺病毒基因组，以形成腺病毒，以形成腺病毒，从而形成腺病毒。我们还将研究DNA损伤蛋白与病毒染色质相互作用的能力，并评估该蛋白对病毒DNA复制的影响。这与对DNA修复反应初始激活的机制的一般理解有关，以及如何通过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。提出的工作也与DNA损伤反应对其他基因组活性（例如DNA复制）的影响有关。该项目所包含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。该项目将为每年大约2名研究生和3-4名本科生提供培训。