Structure and Function of Bacterial RecN Protein

细菌 RecN 蛋白的结构和功能

基本信息

批准号：
8085734
负责人：
SHELLEY LUSETTI
金额：
$ 14.41万
依托单位：
NEW MEXICO STATE UNIVERSITY LAS CRUCES
依托单位国家：
美国
项目类别：
财政年份：
2009
资助国家：
美国
起止时间：
2009-07-24 至 2013-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8085734
关键词：
ATP Hydrolysis ATP phosphohydrolase Bacteria Bacterial Genome Bacterial Model Binding Biochemical Biology C-terminal Chromosomes Coiled-Coil Domain Communication Research Complex Conserved Sequence DNA DNA Damage DNA Double Strand Break DNA Repair DNA Repair Pathway DNA repair protein Deinococcus radiodurans Development Double Strand Break Repair Educational workshop Escherichia coli Genetic Genome Goals Grant Homologous Gene Housing Hydrolysis In Vitro Investigation Kinetics Laboratories Maintenance Manuscripts Mentorship Metabolism Modeling Molecular Mutation Organism Orthologous Gene Physical condensation Pilot Projects Play Positioning Attribute Property Protein Family Proteins Reaction Recombinant Proteins Research Research Personnel Research Proposals Role Sister Chromatid Structure System Testing Training Tumor Suppressor Proteins Universities Wisconsin Work cohesin cohesion ds-DNA enzyme pathway in vivo member post-doctoral training protein complex protein protein interaction public health relevance recombinase repaired stem

项目摘要

DESCRIPTION (provided by applicant): The overall goal of this research proposal is to reveal the molecular function of RecN, a protein critical to the repair of DNA double-stranded breaks (DSBs) in bacteria. Bacterial RecN proteins share significant homology to the Structural Maintenance of Chromosomes (SMC) family of proteins. Eukaryotic SMC proteins have essential (although not fully understood) house keeping and tumor suppressor roles in a variety of DNA metabolic processes such as chromosomal condensation, sister chromatid cohesion and recombinational DNA repair. Although extensive genetic evidence underscores the importance of RecN proteins to bacterial genome maintenance, there has been no substantive biochemical investigation into their function and, consequently, the specific reactions requiring RecN have not been identified. This situation reflects the difficulties encountered in working with the Escherichia coli (a model bacterial organism) RecN protein by several research groups due to insolubility of the over-expressed protein. However, we have identified a RecN homolog that is soluble when expressed in E. coli and are positioned to initiate pilot studies to establish testable hypotheses for the biochemical function of bacterial RecN proteins in recombinational DNA repair pathways. This work will provide valuable models for understanding the molecular role that eukaryotic SMC proteins play in genome maintenance. PUBLIC HEALTH RELEVANCE: Biochemical approaches to provide valuable models for understanding the molecular role that SMC proteins play in genome maintenance and recombinational DNA repair.

描述（由申请人提供）：该研究建议的总体目标是揭示RECN的分子功能，RECN的分子功能是细菌中DNA双链断裂（DSB）至关重要的蛋白质。细菌RECN蛋白与染色体（SMC）蛋白质家族的结构维持具有重要同源性。真核SMC蛋白在多种DNA代谢过程中的抑制（尽管尚不完全了解）的房屋保存和抑制肿瘤作用，例如染色体凝结，姐妹染色体凝聚和重组DNA修复。尽管广泛的遗传证据强调了RECN蛋白对细菌基因组维持的重要性，但尚未对其功能进行实质性的生化研究，因此，尚未鉴定出需要RECN的特定反应。这种情况反映了由于过表达的蛋白质无法溶解性而与几个研究组一起使用大肠杆菌（一种模型细菌生物体）RECN蛋白遇到的困难。但是，我们已经确定了一种在大肠杆菌中表达时可溶的RECN同源物，并定位以启动初步研究，以建立可检验的假设，以实现重组DNA修复途径中细菌RECN蛋白的生化功能。这项工作将为理解真核SMC蛋白在基因组维持中起的分子作用提供宝贵的模型。公共卫生相关性：生化方法提供了有价值的模型，以了解SMC蛋白在基因组维持和重组DNA修复中起的分子作用。