GENOMIC DISTRIBUTION AND PHYLOGENY OF DNA REPAIR

这项提案的总体目标是研究遗传毒性和修复 氧化的DNA碱基 具体目标有两个。 一是 确定碱基切除修复（DNA糖基化酶介导）是否 在活跃转录的基因中具有选择性， UV二聚体的核苷酸切除修复（多蛋白内切核酸酶）。 我们 将研究5-羟甲基尿嘧啶（HmUra）的修复，作为一个例子 不阻断转录的病变。 其次，我们会研究 修复酶、HmUra-DNA糖基化酶和 5-羟甲基胞嘧啶（HmCyt）-DNA糖基化酶。 这两项活动 存在于哺乳动物组织中而不存在于细菌中。 这些是 显示这种系统发育唯一已知的DNA糖基化酶活性 清白的. 对它们的系统发育分布的研究将阐明 甲基胞嘧啶和胸腺嘧啶对内源性 氧化应激 对DNA的氧化损伤被认为是 在癌症和衰老的病因学中的作用。 我们的方法是直接的 生物化学和系统发育研究在评估这一假设。

The overall goal of this proposal is to study the genotoxicity and repair of oxidized DNA bases. The specific aims are two. The first is to determine whether base excision repair (Dna glycosylase mediated) is selective in actively transcribed genes as has been shown for the nucleotide excision repair (multi-protein endo-nuclease) of UV dimers. We will study the repair of 5-Hydroxymethyluracil (HmUra) as an example of a lesion which does not block transcription. Secondly, we will study the phylogenetic distribution of the repair enzymes, HmUra-DNA glycosylase and 5-hydroxymethylcytosine (HmCyt)-DNA glycosylase. Both of these activities are present in mammalian tissue and are absent from bacteria. These are the only known DNA glycosylase activities showing this phylogenetic dissociation. A study of their phylogenetic distribution will clarify the susceptibility of methylcytosine and thymine residues to endogenous oxidative stress. Oxidative damage to DNA has been suggested to play a role in the etiology of cancer and aging. Our approach is a direct biochemical and phylogenetic study addressed at evaluating this hypothesis.