Replication Fork Repair

复制叉修复

• 批准号: 10696070
• 负责人: SUSAN THOMAS LOVETT
• 金额: $ 50.46万
• 依托单位: BRANDEIS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1994
• 资助国家: 美国
• 起止时间: 1994-08-01 至 2026-07-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10696070
• 关键词: Address; Affect; Aging; Antibiotic Resistance; Bacteria; Bacteria sigma factor KatF protein; Base Pairing; Binding; Binding Proteins; Biochemical; Cell Survival; Cells; Closure by clamp; Complex; Copying Processes; DNA; DNA Damage; DNA Polymerase III; DNA Repair; DNA biosynthesis; DNA metabolism; DNA replication fork; DNA-Directed RNA Polymerase; Defect; Development; Electron Transport Complex III; Escherichia coli; Event; Evolution; Genes; Genetic; Genetic Diseases; Genetic Materials; Genetic Transcription; Genome; Genome Stability; Genomic DNA; Genomic Instability; Goals; Gram-Negative Bacteria; Growth; Head; Holoenzymes; Human; Immunologics; Infection; Information Protection; Interruption; Left; Malignant Neoplasms; Mediating; Microscopic; Molecular Biology; Mutation; Neurologic; Nucleotides; Organism; Pathway interactions; Physiology; Play; Premature aging syndrome; Process; Production; Proliferating; Property; Protein Biochemistry; Proteins; RNA; Reaction; Regulatory Pathway; Ribosomal RNA; Role; Signal Transduction; Site; Starvation; Structure; System; Testing; Toxin; Transcript; Transcription Coactivator; Transcriptional Regulation; Virulence Factors; Visualization; Work; cold shock protein; conflict resolution; genetic analysis; genetic approach; helicase; infectious disease treatment; inhibitor; interest; microbial; microorganism; model organism; mutant; novel; pathogenic bacteria; pathogenic microbe; prevent; protein complex; rRNA Operon; recruit; repaired; response; rho; transcription termination

Project Summary Replication fork repair is essential for cell survival and stability of genetic material. In humans, inefficiency of repair is associated with cancer proneness, neurological, immunological, developmental defects and premature aging. For microbial pathogens, the ability to repair DNA damage is required for survival of bacterial pathogens and promotes genetic change that can contribute to antibiotic resistance and persistence of infection. The long-term goal of our studies is a more complete mechanistic understanding of the repair of replication forks and how it affects genomic stability. This will be accomplished using the genetic system of Escherichia coli, whose physiology is well understood. A central interest is how bacterial cells signal difficulties in replication to facilitate repair and how this is integrated with other aspects of bacterial growth. By biochemical and genetic analysis, this work will elucidate how a newly discovered conserved DNA helicase protein, YoaA, interacts with the replisome to overcome barriers in replication. This study will specifically address the influence of RNA transcription and DNA protein complexes on replication and genomic instability and what mechanisms are used to overcome conflicts between replication and transcription machinery. The regulatory pathway controlled by stringent starvation protein, SspA, will also be explored to discover how it impacts DNA metabolism. Because all cells repair DNA in fundamentally similar ways by evolutionarily related pathways, these studies using microbial model organisms should reveal mechanisms applicable to repair of DNA in human cells. In addition, because the DNA damage response in microbial pathogens plays a role in toxin production, antibiotic resistance and persistence of infection, this work could provide new information important for the treatment of infectious disease.

项目总结