Recombinational Mechanisms of DNA Repair

DNA修复的重组机制

基本信息

批准号：
10806579
负责人：
Wolf-Dietrich Heyer
金额：
$ 1.13万
依托单位：
UNIVERSITY OF CALIFORNIA AT DAVIS
依托单位国家：
美国
项目类别：
财政年份：
2000
资助国家：
美国
起止时间：
2000-01-01 至 2026-06-30
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10806579
关键词：
ATRX gene Abbreviations Base Pairing Biochemical Biological Biological Assay Breast Cells Central Nervous System Neoplasms Complement Complex Cruciform DNA DNA DNA Damage DNA Double Strand Break DNA Repair DNA Repair Pathway DNA replication fork DNA-Directed DNA Polymerase Data Defect Double Strand Break Repair Drug Targeting Enzymes Event Funding Genetic Genetic Recombination Genome Stability Genomic Instability Goals Homologous Gene Human In Vitro Incubators Insecta Invaded Ionizing radiation Lead Length Malignant Neoplasms Malignant neoplasm of prostate Maps Measures Mediating Metabolism Modality Modeling Molecular Motor Mutation Nucleotides Outcome Pathway interactions Poly(ADP-ribose) Polymerase Inhibitor Poly(ADP-ribose) Polymerases Process Production Proteins Quality Control RAD54L gene RECQL5 gene Reaction Refrigeration Regulation Research Resolution Role Saccharomyces cerevisiae Saccharomycetales Sister Chromatid Exchange Structure Technology Testing Therapeutic Time Topoisomerase Work Yeasts antitumor agent cancer predisposition cancer therapy cancer type crosslink genetic approach homologous recombination improved insight novel novel therapeutic intervention personalized medicine reconstitution single molecule targeted treatment tumor

项目摘要

Project Summary Homologous recombination (HR) maintains genomic stability through high-fidelity repair of DNA double- stranded breaks (DSB) and other complex DNA damage that is induced directly or indirectly by common anti- tumor agents including ionizing radiation, topoisomerase-targeted drugs, interstrand crosslinking agents, and those causing replication forks stalling. HR defects bear dual significance for cancer by first leading to genomic instability and increased cancer predisposition. Moreover, HR defects cause specific cellular vulnerabilities that can be exploited therapeutically either by traditional DNA damage-based treatment or by targeted treatment for example by poly(ADP-ribose) polymerase inhibition. The overarching goal is to elucidate the mechanisms of HR. This application focuses on a central HR intermediate, the displacement loop (D-loop), which represents the branchpoint for the HR sub-pathways. The Specific Aims are: (1) Define D-loop length in cells and the role of Rdh54 in D-loop metabolism. (2) Delineate the role of human RAD54B in HR. (3) Determine the roles of RECQ1 and RECQ5 in D-loop editing and crossover control. All aims require the use of the requested refrigerated incubator/shaker used for protein production by insect cells in this application.

项目概要同源重组 (HR) 通过 DNA 双链的高保真修复维持基因组稳定性链断裂 (DSB) 和其他复杂的 DNA 损伤是由常见的抗肿瘤药物，包括电离辐射、拓扑异构酶靶向药物、链间交联剂和导致复制叉停止的那些。 HR 缺陷对癌症具有双重意义：首先导致基因组缺陷不稳定和增加癌症易感性。此外，人力资源缺陷会导致特定的细胞脆弱性可以通过传统的基于 DNA 损伤的治疗或针对以下疾病的靶向治疗来进行治疗：例如通过聚（ADP-核糖）聚合酶抑制。总体目标是阐明其机制人力资源。该应用重点关注中心 HR 中间体，即位移环（D 环），它代表 HR 子路径的分支点。具体目标是： (1) 定义细胞中 D 环的长度及其作用 Rdh54 在 D 环代谢中的作用。 (2) 描述人 RAD54B 在 HR 中的作用。 (3) 确定角色 D 环路编辑和交叉控制中的 RECQ1 和 RECQ5。所有目标都需要使用所要求的本应用中用于昆虫细胞生产蛋白质的冷藏培养箱/摇床。