STRUCTURE OF DNA POLYMERASE

遗传物质的复制和修复对所有人来说都是必不可少的 生物和每个物种的生存需要这样做， 及时准确的方式。DNA的合成是一个复杂的，高度 由DNA聚合酶催化的调节反应。对DNA造成的损伤 化学或物理因素引起的致突变前病变。生物 诱变剂或DNA损伤剂的作用取决于 以及当DNA聚合酶遇到DNA时会发生什么 损伤。一个阻碍复制的病变是潜在的致命事件 除非它可以被修复或绕过。与此同时，translesion DNA聚合酶的复制可能导致突变。由于化学 致癌作用通常与加合物或受损部位有关， DNA，DNA聚合酶的研究是高度相关的， 了解致癌作用。 这项研究的长期目标是从分子水平上理解 DNA复制。实现这一目标需要了解 DNA聚合酶结构与功能的关系 这些 功能包括引物与模板DNA的结合，dNTP的结合， 底物，聚合催化，提高聚合效率的机理， 复制的保真度和增加持续合成能力的机制。在 目前，我们对这些过程的理解受到了 完全缺乏B类或α型的结构信息， 聚合酶，包括真核复制型聚合酶，并通过 关于聚合酶的结构数据非常有限。 本研究的主要目的是确定这三个 E.大肠杆菌DNA聚合酶II通过使用 X射线晶体学技术。DNA聚合酶II由DNA诱导 作为SOS反应的一部分， 修复. DNA聚合酶II与真核生物的a型复制有关， 聚合酶，而不是更好地表征E. coli DNA聚合酶I， 因此这种酶是特别感兴趣的。

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.