RIBONUCLEASE H2

核糖核酸酶H2

• 批准号: 7957269
• 负责人: THOMAS J HOLLIS
• 金额: $ 1.35万
• 依托单位: BROOKHAVEN SCIENCE ASSOC-BROOKHAVEN LAB
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-07-01 至 2010-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7957269
• 关键词: Biological; Cell Death; Complex; Computer Retrieval of Information on Scientific Projects Database; Crystallography; DNA; Disease; Functional disorder; Funding; Goals; Grant; Human; Hybrids; Hydrolysis; Immune response; Inherited; Institution; Lead; Light; Multienzyme Complexes; Mutation; Natural Immunity; Pathogenesis; Process; Proteins; RNA; Research; Research Personnel; Resources; Ribonucleases; Source; Synchrotrons; Syndrome; Systemic Lupus Erythematosus; United States National Institutes of Health; disease-causing mutation; nuclease

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Mutations in the RNase H2 proteins are an underlying cause of inherited forms of systemic lupus erythematosus (SLE) and Aicardi-Gouti¿¿res syndrome (AGS), implicating dysfunction of these proteins in an aberrant immune response. Evidence suggests that the pathogenesis of these diseases is likely related to the accumulation of non-processed DNA and RNA intermediates after cell death, which leads to the activation of innate immunity. Human RNase H2 hydrolyzes RNA within RNA:DNA hybrids, but functions as part of a larger, heterotrimeric complex. Thus, it represent a specific example of the general phenomenon that activities of cellular nucleases are often controlled by subunit associations within a larger complex, and that dysfunction of these complexes leads to disease. The goal of this project is to determine how the catalytic activity of this enzyme complex is regulated and how the disease-causing mutations lead to biological dysfunction.

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 RNaseH2蛋白的突变是遗传性系统性红斑狼疮(SLE)和艾卡迪-古提斯综合征(AGS)的潜在原因，这意味着这些蛋白的功能障碍导致了异常的免疫反应。有证据表明，这些疾病的发病机制可能与细胞死亡后未加工的DNA和RNA中间体积聚导致天然免疫激活有关。人类核糖核酸酶H2在RNA：DNA杂交物中对RNA进行水解，但作为更大的异源三聚体复合体的一部分发挥作用。因此，它代表了一个普遍现象的具体例子，即细胞核酸酶的活性通常由较大复合体中的亚单位关联控制，这些复合体的功能障碍导致疾病。该项目的目标是确定这种酶复合体的催化活性是如何调节的，以及致病突变是如何导致生物功能障碍的。