Regulation of V(D)J recombination by Rag2 C terminus
Rag2 C 末端对 V(D)J 重组的调节
基本信息
- 批准号:8073125
- 负责人:
- 金额:$ 33.56万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2010
- 资助国家:美国
- 起止时间:2010-05-20 至 2015-04-30
- 项目状态:已结题
- 来源:
- 关键词:AccountingAcidic RegionAcidsAddressAffectAmino AcidsAntibodiesApplications GrantsB-LymphocytesBindingBiochemicalBiochemistryC-terminalCell Surface ReceptorsCell SurvivalChromatinComplexDNADNA BindingDNA biosynthesisDevelopmentFingersGenerationsGenesGenetic RecombinationGoalsHistone H3HistonesImmune systemImmunoglobulinsImmunologic Deficiency SyndromesJ segment geneLeadLengthLymphocyteLysineMCM2 geneMCM4 geneMediatingModificationMolecularMutationNucleosomesPatientsPlantsPlayPrincipal InvestigatorProcessProteinsRag1 MouseReactionRegulationReportingRoleSeriesSiteSolutionsStretchingT-Cell ReceptorT-LymphocyteV(D)J RecombinationWorkchromatin immunoprecipitationhomeodomainin vivoleukemia/lymphomamutantpathogenprogramsprotein protein interactionprotocol developmentpublic health relevancerecombinaserepairedresearch study
项目摘要
DESCRIPTION (provided by applicant): V(D)J recombination is a site-specific somatic recombination reaction whose end products are genes encoding cell surface receptors and antibody molecules that are central to immune system function. Proper recombination is absolutely required for development of a healthy immune system: when the reaction does not occur or is poorly controlled, there is the potential for development of immunodeficiencies, leukemias, and lymphomas. Our long-term goal is to understand the mechanisms of V(D)J recombination and its regulation, and our approach has been through a biochemical analysis of the RAG proteins. Though much progress has been made in the field of recombination in the last two decades, there are still numerous questions outstanding, among them are the issue of accessibility and the regulation of recombination in vivo. In this grant application, we describe a series of experiments that will address these issues while extending our findings that showed interaction of Rag2 with core histones and the MCM complex. Through specific aims proposed, we will: 1) Investigate the requirement and participation of MCM2-7 complex and MCM associated proteins in V(D)J recombination; 2) Study the role of Rag2 C-terminus, acidic region and PHD domain, in the different steps of V(D)J recombination as well as their participation in the various protein-protein interactions mediated by this region; 3) Analyze the RSS cleavage mechanisms that depend on Rag2 full-length using a chromatin substrate. The focus of these aims is to understand the molecular mechanism that determine regulation of V(D)J recombination by Rag2 and specifically the contribution of Rag2 C-terminus to this process.
PUBLIC HEALTH RELEVANCE: V(D)J recombination is an essential process that takes place in B and T lymphocytes. This process is mediated by recombination factors that play unique and fundamental roles; deregulation of any of the required factors results in severe immunodeficiency. This project is focused on understanding how Rag2, one of the recombination factors, regulated the reaction by mediating multiple protein interactions and thus modulating the generation of a diverse immune system.
描述(由申请人提供):V(D)J重组是一种位点特异性体细胞重组反应,其终产物是编码细胞表面受体和抗体分子的基因,这些受体和抗体分子对免疫系统功能至关重要。正确的重组是健康免疫系统发育所必需的:当反应不发生或控制不良时,有可能发展为免疫缺陷、白血病和淋巴瘤。我们的长期目标是了解V(D)J重组及其调控的机制,我们的方法是通过RAG蛋白的生化分析。尽管在过去的二十年里重组领域取得了很大的进展,但仍然存在许多悬而未决的问题,其中包括可及性问题和体内重组的调控问题。在本申请中,我们描述了一系列实验,这些实验将解决这些问题,同时扩展我们的发现,这些发现表明Rag 2与核心组蛋白和MCM复合物的相互作用。通过提出具体的研究目标,我们将:1)研究MCM 2 -7复合物和MCM相关蛋白在V(D)J重组中的需求和参与:2)研究Rag 2 C端、酸性区和PHD结构域在V(D)J重组的不同步骤中的作用,以及它们在该区域介导的各种蛋白质-蛋白质相互作用中的参与; 3)使用染色质底物分析依赖于Rag 2全长的RSS切割机制。这些目标的重点是了解决定Rag 2调节V(D)J重组的分子机制,特别是Rag 2 C-末端对这一过程的贡献。
公共卫生相关性:V(D)J重组是发生在B和T淋巴细胞中的重要过程。这个过程是由发挥独特和基本作用的重组因子介导的;任何所需因子的失调都会导致严重的免疫缺陷。该项目的重点是了解重组因子之一Rag 2如何通过介导多种蛋白质相互作用来调节反应,从而调节多样化免疫系统的产生。
项目成果
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{{ truncateString('PATRICIA CORTES', 18)}}的其他基金
Regulation of V(D)J recombination by Rag2 C terminus
Rag2 C 末端对 V(D)J 重组的调节
- 批准号:
7781189 - 财政年份:2010
- 资助金额:
$ 33.56万 - 项目类别:
Regulation of V(D)J recombination by Rag2 C terminus
Rag2 C 末端对 V(D)J 重组的调节
- 批准号:
8260320 - 财政年份:2010
- 资助金额:
$ 33.56万 - 项目类别:
Regulation of V(D)J recombination by Rag2 C terminus
Rag2 C 末端对 V(D)J 重组的调节
- 批准号:
8653520 - 财政年份:2010
- 资助金额:
$ 33.56万 - 项目类别:
Regulation of V(D)J recombination by Rag2 C terminus
Rag2 C 末端对 V(D)J 重组的调节
- 批准号:
8458581 - 财政年份:2010
- 资助金额:
$ 33.56万 - 项目类别:
Artemis: Biochemical ,structural and functional analysis
Artemis:生化、结构和功能分析
- 批准号:
7372935 - 财政年份:2009
- 资助金额:
$ 33.56万 - 项目类别:
Artemis: Biochemical ,structural and functional analysis
Artemis:生化、结构和功能分析
- 批准号:
7896656 - 财政年份:2009
- 资助金额:
$ 33.56万 - 项目类别:
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