A Deoxyribozyme, Sero1C, Uses Light and Serotonin to Repair Diverse Pyrimidine Dimers in DNA

Thorne, Rebecca; Chinnapen, Daniel J.‐F.; Sekhon, Gurpreet S.; Sen, Dipankar

doi:10.1016/j.jmb.2009.02.064

Cited by 26 publications

(32 citation statements)

References 45 publications

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“…Likewise, DNA has been evolved in vitro to catalyze a variety of reactions including site-specific phosphodiester cleavage,(9) the Diels−Alder cycloaddition,(17) and light-mediated repair of thymine dimers. 18,19 …”

Section: Introductionmentioning

confidence: 99%

Enhanced Functional Potential of Nucleic Acid Aptamer Libraries Patterned to Increase Secondary Structure

2010

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The in vitro selection of nucleic acid libraries has driven the discovery of RNA and DNA receptors (aptamers) and catalysts with tailor-made functional properties. Functional nucleic acids emerging from selections have been observed to possess an unusually high degree of secondary structure. In this study, we experimentally examined the relationship between the degree of secondary structure in a nucleic acid library and its ability to yield aptamers that bind protein targets. We designed a patterned nucleic acid library (denoted R*Y*) to enhance the formation of stem-loop structures without imposing any specific sequence or secondary structural requirement. This patterned library was predicted computationally to contain a significantly higher average folding energy compared to a standard, unpatterned N60 library of the same length. We performed three different iterated selections for protein binding using patterned and unpatterned libraries competing in the same solution. In all three cases, the patterned R*Y* library was enriched relative to the unpatterned library over the course of the 9- to 10-round selection. Characterization of individual aptamer clones emerging from the three selections revealed that the highest affinity aptamer assayed arose from the patterned library for two protein targets, while in the third case, the highest affinity aptamers from the patterned and random libraries exhibited comparable affinity. We identified the binding motif requirements for the most active aptamers generated against two of the targets. The two binding motifs are 3.4- and 27-fold more likely to occur in the R*Y* library than in the N60 library. Collectively, our findings suggest that researchers performing selections for nucleic acid aptamers and catalysts should consider patterned libraries rather than commonly used Nm libraries to increase both the likelihood of isolating functional molecules and the potential activities of the resulting molecules.

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Section: Introductionmentioning

confidence: 99%

Enhanced Functional Potential of Nucleic Acid Aptamer Libraries Patterned to Increase Secondary Structure

2010

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“…Subsequently, a different deoxyribozyme named Sero1C was identified that cleaves thymine and related dimers by irradiation at an optimal wavelength of 315 nm in the presence of serotonin as an obligatory cofactor, also in the absence of divalent metal ions. [40] All of these results establish that deoxyribozymes can be effective photochemically driven catalysts. Many other experiments are conceivable for using the combination of DNA enzymes and light to catalyze particular chemical reactions.…”

Section: Dna As a Catalystmentioning

confidence: 85%

DNA as a Versatile Chemical Component for Catalysis, Encoding, and Stereocontrol

Silverman

2010

Angew Chem Int Ed

231

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DNA (deoxyribonucleic acid) is the genetic material common to all of Earth's organisms. Our biological understanding of DNA is extensive and well-exploited. In recent years, chemists have begun to develop DNA for nonbiological applications in catalysis, encoding, and stereochemical control. This Review summarizes key advances in these three exciting research areas, each of which takes advantage of a different subset of DNA's useful chemical properties.

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“…A pterin moiety, which is a guanine nucleobase analogue, can replace any of six guanines in UV1C, allowing this deoxyribozyme to use violet light rather than UVB radiation and suggesting potential medical applications in photoreversion therapy [63]. The Sen lab also reported the Sero1C deoxyribozyme, which catalyzes thymine dimer photoreversion using serotonin as a discrete small-molecule cofactor [64]. In Sero1C, the indole ring of serotonin (rather than a G-quadruplex of the deoxyribozyme itself) serves as an antenna to enable thymine dimer photocleavage.…”

Section: Reaction Scope Of Catalysis By Dnamentioning

confidence: 99%

Catalytic DNA: Scope, Applications, and Biochemistry of Deoxyribozymes

Silverman

2016

Trends in Biochemical Sciences

309

215

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The discovery of natural RNA enzymes (ribozymes) prompted the pursuit of artificial DNA enzymes (deoxyribozymes) by in vitro selection methods. A key motivation is the conceptual and practical advantages of DNA relative to proteins and RNA. Early studies focused on RNA-cleaving deoxyribozymes, and more recent experiments have expanded the breadth of catalytic DNA to many other reactions. Including modified nucleotides has the potential to widen the scope of DNA enzymes even further. Practical applications of deoxyribozymes include their use as sensors for metal ions and small molecules. Structural studies of deoxyribozymes are just beginning; mechanistic experiments will surely follow. From the first report 21 years ago, the field of deoxyribozymes has promise for both fundamental and applied advances in chemistry, biology, and other disciplines.

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A Deoxyribozyme, Sero1C, Uses Light and Serotonin to Repair Diverse Pyrimidine Dimers in DNA

Cited by 26 publications

References 45 publications

Enhanced Functional Potential of Nucleic Acid Aptamer Libraries Patterned to Increase Secondary Structure

Enhanced Functional Potential of Nucleic Acid Aptamer Libraries Patterned to Increase Secondary Structure

DNA as a Versatile Chemical Component for Catalysis, Encoding, and Stereocontrol

Catalytic DNA: Scope, Applications, and Biochemistry of Deoxyribozymes

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