DNA POLYMERASE ETA/DNA/DNTP COCRYSTALS: A LARGE UNIT CELL PROBLEM

这个子项目是利用资源的许多研究子项目之一。 由NIH/NCRR资助的中心拨款提供。对子项目的主要支持 子项目的首席调查员可能是由其他来源提供的， 包括美国国立卫生研究院的其他来源。为子项目列出的总成本可能 表示该子项目使用的中心基础设施的估计数量， 不是由NCRR赠款提供给次级项目或次级项目工作人员的直接资金。 所有生物的生存在很大程度上取决于忠实复制DNA的能力。细胞DNA不断受到损伤剂的影响，各种DNA修复途径已经进化出来修复由此造成的损伤。在DNA复制过程中，细胞如何绕过这些损伤一直是DNA复制、突变和致癌领域的一个关键问题。这个长期存在的难题的答案直到最近才随着DNA聚合酶ETA(PolETA)的发现而来，这是一个新的跨病变DNA合成(TLS)聚合酶家族的原型。Pol ETA在真核DNA聚合酶中是独一无二的，因为它能够通过紫外光诱导的顺式环丁烷胸腺嘧啶-胸腺嘧啶二聚体(T-T)通过插入两个与二聚体相反的腺嘌呤进行复制。人类POL ETA的突变是一种遗传性癌症易感性疾病，即变种形式的着色性干皮病(XP-V)。因此，POL ETA是第一个被证明在人类身上发挥肿瘤抑制作用的DNA聚合酶。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. The survival of all organisms depends critically on the ability to faithfully replicate DNA. Cellular DNA is continually subjected to damaging agents and a variety of DNA repair pathways have evolved to repair the resulting lesions. How cells bypass these lesions during DNA replication has been a key question in the areas of DNA replication, mutagenesis, and carcinogenesis. The answer to this longstanding puzzle came only recently with the discovery of DNA polymerase eta (Pol eta), a prototype of a new family of translesion DNA synthesis (TLS) polymerases. Pol eta is unique amongst eukaryotic DNA polymerases in its proficient ability to replicate through a UV-induced cis-syn cyclobutane thymine-thymine (T-T) dimer by inserting two adenines opposite the dimer. Mutations in human Pol eta are responsible for an inherited cancer-prone disorder, the variant form of xeroderma pigmentosum (XP-V). Pol eta is, thus, the first DNA polymerase demonstrated to act as a tumor suppressor in humans.