STRUCTURE OF DNA POLYMERASE

遗传物质的复制和修复对所有人都是必不可少的 生物体和每个物种的生存需要在 及时准确的时尚。DNA的合成是一种复杂的、高度 DNA聚合酶催化的调节反应。对DNA造成的损伤 由化学或物理因素引起的预致突变损伤。生物学的 诱变剂或DNA损伤剂的效果取决于两者的效率 DNA修复以及当DNA聚合酶遇到DNA时会发生什么 损伤。阻止复制的病变可能是致命的事件 除非它能被修复或绕过。同时，跨损伤 DNA聚合酶的复制可能导致突变。既然是化学 癌变通常与加合物或受损部位有关。 DNA，对DNA聚合酶的研究与 对癌症发生的理解。 这项拟议的研究的长期目标是了解分子 DNA复制。要实现这一目标，需要了解 DNA聚合酶结构与功能的关系这些 功能包括结合引物和模板DNA，结合dNTP 底物，聚合催化，改善的机理 复制的保真度和提高加工性的机制。在 目前，我们对这些过程的理解受限于 完全缺乏关于B类或阿尔法型的结构信息， 包括真核复制聚合酶的聚合酶和 一般来说，关于聚合酶的结构数据非常有限。 拟议研究的主要目的是确定这三个 大肠杆菌DNA聚合酶II的空间结构 X射线结晶学技术。DNA聚合酶II是由DNA诱导的 Dazzle作为SOS反应的一部分，似乎在DNA中发挥作用 修理。DNA聚合酶II与真核生物的a型复制有关 聚合酶而不是特征更好的大肠杆菌DNA聚合酶I， 因此，这种酶特别有价值。

The replication and repair of genetic material is essential for all organisms and the survival of each species requires that this be done in a timely and accurate fashion. The synthesis of DNA is a complex, highly regulated reaction catalyzed by DNA polymerases. Damage to the DNA caused by chemical or physical agents causes premutagenic lesions. The biological effects of mutagens or DNA damaging agents depend on both the efficiency of DNA repair and what occurs when a DNA polymerase encounters the DNA lesion. A lesion that blocks replication is potentially a lethal event unless it can be repaired or bypassed. At the same time, translesion replication by a DNA polymerase may lead to mutation. Since chemical carcinogenesis is generally associated with adducts or damaged sites in the DNA, the study of DNA polymerases is highly relevant to an understanding of carcinogenesis. The long range goal of the proposed research is a molecular understanding of DNA replication. Attaining this goal requires a knowledge of the relationship between DNA polymerase structure and its functions. These functions include the binding of primer and template DNA, binding of dNTP substrates, the catalysis of polymerization, mechanisms for improving the fidelity of replication and mechanisms for increasing processivity. At the present time our understanding of these processes is limited by the complete lack of structural information on the class B, or alpha-type, polymerases that include the eukaryotic replicative polymerases and by the very limited structural data on polymerases in general. The primary aim of the proposed research is the determination of the three dimensional structure of the E. coli DNA polymerase II through the use of X-ray crystallographic techniques. DNA polymerase II is induced by DNA dazzle as part of the SOS response and appears to have a role in DNA repair. DNA polymerase II is related to the eukaryotic a type replicative polymerases rather than the better characterized E. coli DNA polymerase I, consequently this enzyme is of particular interest.