SEQUENCE CONTEXT DEPENDENT EXCISION AND MUTAGENESIS

序列上下文相关的切除和诱变

• 批准号: 6378050
• 负责人: TIMOTHY R O'CONNOR
• 金额: $ 27.56万
• 依托单位: BECKMAN RESEARCH INSTITUTE/CITY OF HOPE
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-09-30 至 2003-09-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6378050
• 关键词: DNA damage; DNA repair; N glycosidase; adduct; animal genetic material tag; endonuclease; enzyme activity; human genetic material tag; hypoxanthines; nucleic acid sequence; oligonucleotides; plasmids; site directed mutagenesis

Sequence context dependent (SCD) effects are involved in the process of mutagenesis and define mutational hotspots in tumors, but little is known about such effects, except as mutational outcomes. The experiments in this proposal will rigorously examine SCD effects in excision and mutagenesis that would contribute to mutational hotspots. Initially, we will establish SCD rules for DNA glycosylase excision. Once the rules are elucidated, our hypotheses regarding the physical-chemical factors governing SCD excision rules for DNA glycosylases will mold the experimental design. Finally, by varying the sequence contiguous to a unique lesion, we will evaluate the role of SCD effects on mutagenesis. The studies proposed will answer important biological questions concerning factors influencing mutation, the quality of mutation databases for tumors, and the mutability of a particular base that could lead to cancer.

序列上下文依赖性（SCD）效应涉及诱变过程并定义肿瘤中的突变热点，但对这种影响知之甚少，除了突变结果。该提案中的实验将严格检查切除和诱变中的SCD效应，这将导致突变热点。最初，我们将建立DNA糖基酶切除酶的SCD规则。一旦阐明了规则，我们关于DNA糖基酶的SCD切除规则的物理化学因素的假设将塑造实验设计。最后，通过将序列与独特的病变相邻改变，我们将评估SCD对诱变的作用。提出的研究将回答有关影响突变的因素，肿瘤突变数据库的质量以及可能导致癌症的特定碱的突变性的重要生物学问题。