DNA与紫外线的相遇：自我保护的本能？,Accounts of Chemical Research

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DNA与紫外线的相遇：自我保护的本能？
Accounts of Chemical Research ( IF 16.4 ) Pub Date : 2018-02-08 00:00:00 , DOI: 10.1021/acs.accounts.7b00582
Adam Barlev ₁ , Dipankar Sen ₁

Affiliation

光化学修饰是DNA（所有自由生存生物的遗传物质）遭受的主要环境损害类别。光解酶是对暴露于紫外线的DNA中形成的共价嘧啶二聚体进行直接光化学修复（光活化）的酶。在1980年代，催化性RNA的发现导致了“ RNA世界假说”，该假说认为，RNA或类似聚合物在进化的早期就同时具有遗传和催化功能。受到RNA世界假说的吸引，我们着手测试是否可以考虑具有光裂解酶活性的催化性RNA（或替代物，催化性DNA）。从随机序列DNA库中进行体外选择会产生两种DNA酶（DNAzyme）：需要血清素作为专性辅因子的Sero1C和UV1C，它与辅因子无关，可以最佳地使用300-310 nm波长的光修复缺口的DNA底物中的环丁烷胸腺嘧啶二聚体。Sero1C和UV1C都显示出多种更新动力学，UV1C修复其底物的量子产率约为0.05，与某些类型的光裂解酶的量子产率相同。对UV1C的深入研究表明，其催化核心由位于结合底物的胸腺嘧啶二聚体近端的鸟嘌呤四链体（G-四链体）组成。我们假设从UV1C的G-四链体中的光激发鸟嘌呤转移电子负责底物的光活化，类似于电子从自然光裂解酶中的光激发黄素辅因子转移到DNA底物中的嘧啶二聚体。

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DNA’s Encounter with Ultraviolet Light: An Instinct for Self-Preservation?

Photochemical modification is the major class of environmental damage suffered by DNA, the genetic material of all free-living organisms. Photolyases are enzymes that carry out direct photochemical repair (photoreactivation) of covalent pyrimidine dimers formed in DNA from exposure to ultraviolet light. The discovery of catalytic RNAs in the 1980s led to the “RNA world hypothesis”, which posits that early in evolution RNA or a similar polymer served both genetic and catalytic functions. Intrigued by the RNA world hypothesis, we set out to test whether a catalytic RNA (or a surrogate, a catalytic DNA) with photolyase activity could be contemplated. In vitro selection from a random-sequence DNA pool yielded two DNA enzymes (DNAzymes): Sero1C, which requires serotonin as an obligate cofactor, and UV1C, which is cofactor-independent and optimally uses light of 300–310 nm wavelength to repair cyclobutane thymine dimers within a gapped DNA substrate. Both Sero1C and UV1C show multiple turnover kinetics, and UV1C repairs its substrate with a quantum yield of ∼0.05, on the same order as the quantum yields of certain classes of photolyase enzymes. Intensive study of UV1C has revealed that its catalytic core consists of a guanine quadruplex (G-quadruplex) positioned proximally to the bound substrate’s thymine dimer. We hypothesize that electron transfer from photoexcited guanines within UV1C’s G-quadruplex is responsible for substrate photoreactivation, analogous to electron transfer to pyrimidine dimers within a DNA substrate from photoexcited flavin cofactors located within natural photolyase enzymes.

更新日期：2018-02-08

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