专题：Nature系列
紫外线的穿透辐射诱导皮肤细胞中的DNA病灶，它们会阻止DNA复制和引起能发展成癌症的突变。身体应对这种损伤的一种方式涉及专门化的DNA聚合酶，以此来绕过这样的病灶。“DNA聚合酶η” (Polη)通过复制含有胸腺嘧啶二聚物的DNA来做这件事，而这种酶的失活导致被称为“着色性干皮病”的皮肤病的一个变种和皮肤癌的高发病率。现在，两个小组确定了Polη的晶体结构。这些结构（一个是酵母酶的结构，一个是人体酶的催化区域的结构）显示了尺寸较大的胸腺嘧啶二聚物在一个异常大的活性点上是怎样被容纳的、以及病灶是怎样通过在其他聚合酶中不存在的相互作用来稳定的。
“着色性干皮病”患者的“错义突变”被发现会破坏聚合酶在正常B形式中维持受损DNA的能力。在配发的News & Views文章中，Suse Broyde 和 Dinshaw Patel讨论了Polη的结构与所报道的其他Y-家族DNA聚合酶结构的相符性问题。（生物谷Bioon.net）
生物谷推荐原文出处：
Nature doi:10.1038/nature09104
Structural basis for the suppression of skin cancers by DNA polymerase η
Timothy D. Silverstein,Robert E. Johnson,Rinku Jain,Louise Prakash,Satya Prakash& Aneel K. Aggarwal
DNA polymerase η (Polη) is unique among eukaryotic polymerases in its proficient ability for error-free replication through ultraviolet-induced cyclobutane pyrimidine dimers, and inactivation of Polη (also known as POLH) in humans causes the variant form of xeroderma pigmentosum (XPV). We present the crystal structures of Saccharomyces cerevisiae Polη (also known as RAD30) in ternary complex with a cis-syn thymine-thymine (T-T) dimer and with undamaged DNA. The structures reveal that the ability of Polη to replicate efficiently through the ultraviolet-induced lesion derives from a simple and yet elegant mechanism, wherein the two Ts of the T-T dimer are accommodated in an active site cleft that is much more open than in other polymerases. We also show by structural, biochemical and genetic analysis that the two Ts are maintained in a stable configuration in the active site via interactions with Gln?55, Arg?73 and Met?74. Together, these features define the basis for Polη’s action on ultraviolet-damaged DNA that is crucial in suppressing the mutagenic and carcinogenic consequences of sun exposure, thereby reducing the incidence of skin cancers in humans.
