Repair of Clustered DNA Damages

修复DNA簇损伤

• 批准号: 7656963
• 负责人: YOKE W KOW
• 金额: $ 22.75万
• 依托单位: EMORY UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-04-01 至 2009-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7656963
• 关键词: Adopted; Affect; Alleles; Area; Attention; Base Excision Repairs; Biological; Biological Assay; Biological Models; Biological Process; Bypass; Cell physiology; Cells; Chromosomes; Class; Complex; Cyclobutanes; DNA; DNA Damage; DNA Ligases; DNA Repair; DNA Repair Enzymes; DNA Repair Pathway; DNA biosynthesis; DNA glycosylase; DNA lesion; DNA repair protein; DNA-Binding Proteins; DNA-Directed DNA Polymerase; Data; Databases; Excision; Frameshift Mutation; Frequencies; Generations; Genes; Genomic Instability; In Vitro; Individual; Ionizing radiation; Lead; Left; Lesion; Measures; Monitor; Mus; Mutation; Nature; Nucleotide Excision Repair; Nucleotides; Oligonucleotides; Pathway interactions; Polymerase; Process; Proteins; Pyrimidine; Pyrimidines; Reactive Oxygen Species; Role; Saccharomyces cerevisiae; Single base substitution; Site; Specificity; Structure; TP53 gene; Techniques; Yeasts; abstracting; base; cancer type; cell transformation; crosslink; in vivo; insight; interest; member; mutant; oxidative DNA damage; plasmid DNA; repair enzyme; repaired

Project Summary/Abstract Clustered DNA damage is a unique class of DNA lesion generated by ionizing radiation. This class of DNA lesion consists of multiple DNA damage in close proximity to each other. Inappropriate processing of clustered lesion by cellular processes can lead to increased lethality and genomic instability in cells. Tandem base damage is a simple member of clustered lesion. Tandem lesions are processed via two major DNA repair pathways, the base excision and nucleotide excision repair pathway. However, incomplete repair of tandem base lesion occurs when the lesion is processed by DNA glycosylases, members of the base excision repair pathway. These data suggest that other DNA repair enzymes or factors are crucial for the subsequent complete repair of tandem base lesions. Saccharomyces cerevisiae or Baker ¿s yeast is a powerful model system for understanding the in vivo processing of tandem lesions. We have adopted and modified the single strand oligonucleotide transformation assay in yeast, allowing us to systematically examine the mechanism by which yeast process tandem lesions. Tandem lesions are introduced into yeast chromosomal DNA by transformation using single stranded oligonucleotide containing unique tandem lesion. Three aims are included in this application. The first aim is directed to examine the mechanism and pathway by which tandem lesions are repaired. The second aim is devoted to determine the mutagenic potential of unrepaired tandem lesion. The third aim is directed to investigate the role of DNA polymerases and other DNA repair factors that are essential for the removal of remaining DNA lesion after the incomplete processing of tandem lesion by DNA glycosylases. Completion of these three aims is expected to provide significant understanding on how cells process tandem lesions and the biological consequences of incompletely repaired tandem lesions.

项目摘要/摘要 聚集的DNA损伤是通过电离产生的独特的DNA病变 辐射。这类DNA病变由多个DNA损伤近距离损伤 彼此。通过细胞过程对聚类病变的不适当处理可以 导致细胞中的致死性和基因组不稳定性增加。串联基本伤害是 簇状病变的简单成员。串联病变通过两个主要DNA处理 维修途径，基本惊喜和核苷酸惊喜修复途径。然而， 当病变通过DNA处理时，会发生串联碱病变的不完全修复 糖基酶，基本惊喜维修途径的成员。这些数据表明 其他DNA修复酶或因素对于随后的完整修复至关重要 串联碱病变。酿酒酵母或面包师的酵母是一种强大的型号 了解串联病变体内处理的系统。我们已经采用了 并修改了酵母中的单链寡核苷酸转化测定法，使我们 系统地检查酵母菌过程串联病变的机制。 串联病变通过使用使用转化引入酵母染色体DNA 单链寡核苷酸含有独特的串联病变。三个目标是 包含在此应用程序中。第一个目的是指研究机制和 串联病变修复的途径。第二个目标是为了确定 未修复的串联病变的诱变潜力。第三个目标是指 研究必不可少的DNA聚合酶和其他DNA修复因子的作用 串联处理不完整后，去除剩余的DNA病变 DNA糖基酶病变。这三个目标的完成将提供 对细胞如何处理串联病变和生物学的深入了解 未完全修复的串联病变的后果。