ADP-RIBOSYL TRANSFERASE

ADP-核糖基转移酶

• 批准号: 8363370
• 负责人: John M Pascal
• 金额: $ 0.96万
• 依托单位: BROOKHAVEN SCIENCE ASSOC-BROOKHAVEN LAB
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-07-01 至 2012-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8363370
• 关键词: Cell Death; Cells; Chromatin; Complex; Crystallography; DNA; DNA Binding; DNA Damage; DNA Repair; DNA Structure; DNA strand break; Data; Detection; Enzymes; Funding; Genome; Goals; Grant; Light; Molecular; National Center for Research Resources; Pathway interactions; Principal Investigator; Research; Research Infrastructure; Resources; Source; Structure; Synchrotrons; Testing; Transcriptional Regulation; Transferase; United States National Institutes of Health; base; cancer therapy; cost; design; inhibitor/antagonist; mutant; novel strategies; repaired

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. ADP-ribosyl transferase (ADPRT), also known as PARP-1, is a chromatin-associated enzyme that functions in DNA repair, transcriptional regulation, and controlled cell death. ADPRT initiates a DNA damage detection and repair pathway that corrects breaks in the structure of DNA, thereby functioning to maintain the integrity and stability of our genomes. Inhibitors of ADPRT sensitize cells to DNA-damaging agents used in cancer therapy; therefore ADPRT has emerged as a promising target for cancer treatment. The catalytic activity of ADPRT is dramatically stimulated by DNA strand breaks. Our objective is to structurally define the molecular mechanism of ADPRT activation. Understanding the mechanism of activation might reveal novel strategies for controlling ADPRT activity. We are currently focusing on a DNA-binding fragment of ADPRT in complex with DNA. The mode of DNA binding is currently unknown. Our data will be used to design structure-based mutants that test the function of this domain of ADPRT. Our long-term goals are to understand how ADPRT recognizes breaks in DNA structure, how DNA binding triggers ADPRT catalytic activity, and how ADPRT activation initiates DNA damage repair.

该副本是利用资源的众多研究子项目之一 由NIH/NCRR资助的中心赠款提供。对该子弹的主要支持 而且，副投影的主要研究员可能是其他来源提供的 包括其他NIH来源。 列出的总费用可能 代表subproject使用的中心基础架构的估计量， NCRR赠款不直接向子弹或副本人员提供的直接资金。 ADP-核糖基转移酶（ADPRT），也称为PARP-1，是一种与染色质相关的酶，在DNA修复，转录调控和受控细胞死亡中起作用。 ADPRT启动了DNA损伤检测和修复途径，该途径纠正了DNA结构的断裂，从而发挥了作用，以维持基因组的完整性和稳定性。 ADPRT的抑制剂使细胞对癌症治疗中使用的DNA受损剂的敏感性；因此，ADPRT已成为癌症治疗的有希望的靶标。 DNA链断裂刺激了ADPRT的催化活性。 我们的目标是在结构上定义ADPRT激活的分子机制。 了解激活的机制可能揭示了控制ADPRT活动的新策略。 我们目前正在专注于与DNA复杂的ADPRT的DNA结合片段。 DNA结合的模式目前未知。 我们的数据将用于设计基于结构的突变体，以测试ADPRT该域功能的功能。 我们的长期目标是了解ADPRT如何识别DNA结构中的断裂，DNA结合如何触发ADPRT催化活性以及ADPRT激活如何启动DNA损伤修复。