A team of researchers from Shandong Normal University in Jinan,中国开发了一种检测尿嘧啶DNA糖基化酶的高灵敏度无标签检测方法。a DNA repair enzyme that removes uracil from DNA molecules.尿嘧啶是一种RNA碱基，and when uracil appears in DNA through deamination of cytosine or misincorporation during DNA synthesis,the error can have mutagenic consequences.
Diminished activity of uracil-DNA glycosylase has been linked to a number of disease states including human immunodeficiency and Bloom syndrome,an inherited disorder associated with an increased risk of cancer (among other symptoms).开发定量尿嘧啶DNA糖基化酶的敏感方法将有助于早期诊断此类疾病，并提高对DNA修复机制的理解。作为概念的证明，研究人员表明，这种方法可以定量分析希拉癌细胞裂解液中的酶。
Their method reminds me of Rube Goldberg machines,which achieve a task via a series of connected,机械步骤。一个步骤的完成会触发另一个步骤的开始：例如一排多米诺骨牌掉落到大理石上，in turn,rolls down a track.In this work the action of one enzyme returns a product that is the preferred substrate of another enzyme.At the risk of deviating slightly,one of the more spectacular examples of a Rube Goldberg machine is seen in the music video for OK GO's ‘this too shall pass',a single-take shoot of a warehouse sized machine,以滚动车为特色，swinging pianos,流水和滚球，all to perform the task of (spoiler alert) blasting the band members in the face with coloured paint.
The strategy starts with the action of uracil-DNA glycosylase and ends with a bioluminescent signal via a cascade of enzymatic reactions
作者的策略包括使用七种不同酶和三种核酸探针的一系列连续步骤。It begins with a double stranded DNA probe containing one rogue uracil base: the perfect bait for uracil-DNA glycosylase.The action of this enzyme and two others,in a process involving base excision,DNA backbone cleavage and the addition of thymine-rich sequences,产生大量的单链DNA分子，其尾部富含胸腺嘧啶。这些分子与富含腺嘌呤的RNA探针杂交生成RNA-DNA双链体。一种酶消化RNA部分，releasing adenosine monophosphate monomers,which are converted to adenosine triphosphate (ATP),a required energy input to activate firefly luciferase.荧光素酶催化荧光素氧化形成氧化荧光素，伴随着一个大型生物发光信号。Thus,uracil-DNA glycosylase is detected with 1-2 orders of magnitude more sensitivity than state-of-the-art fluorescent and luminescent assays.
与传统的rube goldberg机器不同，which are characterised by unnecessary complexity,in this ‘enzymatic Rube Goldberg machine' each step has a specific purpose and serves to amplify the signal of the last.这被称为“三环级联信号放大”，它使酶的高度敏感检测。
To find out more please read:
Yan Zhang,Qing-nan Li,陈陈丽，陈杨章。
Chem.Commun.,2018，五十四,6991-6994
DOI: 10.1039/c8cc03769h
About the author
Zoë Hearne is a PhD candidate in 新利手机客户端chemistry at McGill University in Montréal,Canada,under the supervision of Professor Chao-Jun Li.She hails from Canberra,澳大利亚，在那里她完成了她的本科学位。Her current research focuses on transition metal catalysis to effect novel transformations,在实验室之外，她是一位热情的化学导师和科学传播者。新利手机客户端新利手机客户端
