MECHANISMS OF P53 MUTAGENESIS

P53 诱变机制

基本信息

批准号：
2769833
负责人：
GERALD P HOLMQUIST
金额：
$ 148.98万
依托单位：
BECKMAN RESEARCH INSTITUTE/CITY OF HOPE
依托单位国家：
美国
项目类别：
财政年份：
1996
资助国家：
美国
起止时间：
1996-09-01 至 2000-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/2769833
关键词：
carcinogenesis gene mutation molecular oncology tumor suppressor genes

项目摘要

Our overall goal is to dissect the molecular components of somatic mutagenesis and incorporate these into a sound rationale for the molecular epidemiology of cancer. Our specific goal is to determine the effect of suspected environmental and endogenous mutagens on the molecular epidemiology of p53 mutations. Using a variety of mutagens, we will map patterns of mutagenesis along each nucleotide position of the p53 gene exons 5-9. The patterns of mutagenesis metrics involve base positions which are heavily damaged or slowly repaired and occur predominantly in those patients who are least proficient at repairing the suspected class of lesions. We will search for a correlation between a mutagenesis metric which forms the pattern and components of each mutagen's mutational signature in the p53 tumor mutation data. Our procedural theme for relating the components of mutageneses involves having four projects concentrating on mapping various molecular phenomena along only one gene, p53, and to thoroughly understand for the first time how these molecular phenomena are interrelated in their determination of mutation frequency. The theme of operations is to facilitate this technology so that mapping of molecular properties will get accomplished. The four projects exploring the mutagenesis mechanisms are: 1) Mechanisms of Ultraviolet Light-Induced p53 Mutations; 2) Mechanisms of Chemical Carcinogen-Induced p53 Mutations; 3) Mechanisms of Oxidative Damage- Induced p53 Mutations; and 4) Base Excision Repair and Alkylating Chemotherapeutic Agent-Induced p53 Damage. The four experimental projects are supported by three cores. The first core will be coordinating and sharing common reagents and for developing and automating the ligation-mediated PCR, the second is for tissue culture, and the third is for administration of the program.

我们的总体目标是剖析躯体的分子成分诱变并将其纳入分子的声音原理中癌症流行病学。我们的具体目标是确定可疑的环境和内源性诱变剂在分子上 p53突变的流行病学。使用各种诱变剂，我们将映射沿p53基因的每个核苷酸位置的诱变模式外显子5-9。诱变指标的模式涉及基础位置严重损坏或缓慢修复，主要发生那些精通可疑类的患者病变。我们将搜索诱变度量的相关性哪个形成了每个诱变者突变的模式和组成部分 p53肿瘤突变数据中的签名。我们关联诱变组成部分的程序主题涉及有四个项目集中于映射各种分子现象仅沿着一个基因p53，并首次彻底理解这些分子现象如何在确定它们的确定突变频率。操作的主题是促进这一点技术以使分子特性的映射能够完成。探索诱变机制的四个项目是：1）机制紫外线诱导的p53突变； 2）化学机制致癌诱导的p53突变； 3）氧化损伤的机制 - 诱导p53突变； 4）碱性切除修复和烷基化化学治疗剂诱导的p53损伤。这四个实验项目得到了三个核心的支持。第一个核心将协调和共享共同的试剂，并用于开发并自动化连接介导的PCR，第二个是用于组织文化，第三个是为了管理该计划。