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

这个子项目是许多利用 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 所有生物体的生存关键取决于忠实复制DNA的能力。 细胞DNA不断受到损伤剂的影响，并且已经进化出多种DNA修复途径来修复所产生的损伤。细胞如何在DNA复制过程中绕过这些损伤一直是DNA复制、诱变和致癌领域的关键问题。 这个长期存在的难题的答案直到最近才随着DNA聚合酶eta（Pol eta）的发现而出现，这是一个新的跨损伤DNA合成（TLS）聚合酶家族的原型。 Pol eta在真核DNA聚合酶中是独特的，其熟练的复制能力通过UV诱导的顺式-顺式环丁烷胸腺嘧啶-胸腺嘧啶（T-T）二聚体通过插入两个腺嘌呤相对于二聚体。 人类Pol eta基因突变导致一种遗传性易患癌症的疾病，即着色性干皮病（XP-V）的变异形式。 因此，Pol eta是第一个被证明在人类中作为肿瘤抑制因子的DNA聚合酶。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. 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.