專題：Nature系列
紫外線的穿透輻射誘導(dǎo)皮膚細胞中的DNA病灶，它們會阻止DNA復(fù)制和引起能發(fā)展成癌癥的突變,。身體應(yīng)對這種損傷的一種方式涉及專門化的DNA聚合酶，以此來繞過這樣的病灶,。“DNA聚合酶η” (Polη)通過復(fù)制含有胸腺嘧啶二聚物的DNA來做這件事,，而這種酶的失活導(dǎo)致被稱為“著色性干皮病”的皮膚病的一個變種和皮膚癌的高發(fā)病率?，F(xiàn)在,，兩個小組確定了Polη的晶體結(jié)構(gòu),。這些結(jié)構(gòu)（一個是酵母酶的結(jié)構(gòu),，一個是人體酶的催化區(qū)域的結(jié)構(gòu)）顯示了尺寸較大的胸腺嘧啶二聚物在一個異常大的活性點上是怎樣被容納的,、以及病灶是怎樣通過在其他聚合酶中不存在的相互作用來穩(wěn)定的。
“著色性干皮病”患者的“錯義突變”被發(fā)現(xiàn)會破壞聚合酶在正常B形式中維持受損DNA的能力,。在配發(fā)的News & Views文章中,，Suse Broyde 和 Dinshaw Patel討論了Polη的結(jié)構(gòu)與所報道的其他Y-家族DNA聚合酶結(jié)構(gòu)的相符性問題。（生物谷Bioon.net）
生物谷推薦原文出處：
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.
