Translesion Synthesis Opposite Carcinogen Bound DNA

跨损伤合成相反致癌物结合 DNA

基本信息

批准号：
7270480
负责人：
ROBERT L EOFF
金额：
$ 4.88万
依托单位：
VANDERBILT UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2006
资助国家：
美国
起止时间：
2006-08-01 至 2009-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7270480
关键词：
2&apos -deoxycytidine 5&apos -triphosphate Address Aging-Related Process Amides Base Pairing Biochemistry Bypass Carcinogens Cell Death Cell division Cells Class Collaborations Complex Crystallography DNA DNA Binding DNA Damage DNA Modification Process DNA Polymerase beta DNA biosynthesis DNA lesion DNA-Directed DNA Polymerase Defense Mechanisms Depth Deuterium Environment Enzymes Event Exonuclease Exposure to Family Fellowship Figs - dietary Gene Mutation Genetic Code Genomics Guanine Hydrogen In Vitro Individual Kinetics Knowledge Lead Lesion Life Light Longevity Malignant Neoplasms Mass Spectrum Analysis Measures Metals Methodology Mitosis Modeling Modification Molecular Motors Mutation Nature O(6)-benzylguanine Organism Play Polymerase Positioning Attribute Process Rate Reaction Research Proposals Role Series Site Source Spectrometry Staging Structure Sulfolobus solfataricus System Techniques Thinking Work base cancer type carcinogenesis day experience fascinate human disease improved insight interest repaired tumorigenesis

项目摘要

DESCRIPTION (provided by applicant): Our bodies are subjected to a barrage of potentially damaging agents every day. Some of these agents come from the environment surrounding us and some are generated inside us by the very act of living. Fortunately for our longevity, systems have evolved within our cells that repair much of the damage that we experience. One of the last lines of defense against permanent damage to our genetic code resides in a class of enzymes called the Y-family polymerases. These molecular motors are unique in their ability to deal with damaged DNA. However, given the veritable jungle of types of DNA lesions, there are many things that we do not yet understand concerning how the Y-family polymerases repair damage. In an effort to address the myriad of unanswered questions regarding Y-family polymerase bypass of damaged DNA, this proposal will study the ability of a model Y-family polymerase called Dpo4 to copy past a very common form of DNA damage that results from exposure to agents that are not only found in the environment but are also used in chemotherapeutic regimes to treat multiple types of cancer. Kinetic analyses will be combined with x-ray crystallographic studies in order to couple structure with function.

描述（由申请人提供）：我们的身体每天都会遭受潜在破坏性特工的弹幕。这些特工中的一些来自我们周围的环境，其中一些是由于生活的行为而产生的。幸运的是，对于我们的寿命，系统已经在我们的细胞中进化，以修复我们遇到的许多损害。防御对我们遗传代码的永久损害的最后防御线之一是一类称为Y-家庭聚合酶的酶。这些分子电动机在处理受损DNA的能力方面是独一无二的。但是，鉴于DNA病变类型的丛林丛林，关于Y-家庭聚合酶如何修复损害，我们尚不了解很多事情。为了解决有关Y型聚合酶绕过受损DNA的无数尚未解决的问题，该建议将研究Y型Y模型 - 家庭聚合酶DPO4的能力，即DPO4复制经过一种非常常见的DNA损害，该DNA损害是由于环境中不仅在化学疗法中使用的多种类型的多种类型的多种类型的癌症所带来的药物而导致的。动力学分析将与X射线晶体学研究结合使用，以便将结构与功能结合。