A Deoxyribozyme That Harnesses Light to Repair Thymine Dimers in DNA

In vitro selection was used to investigate whether nucleic acid enzymes are capable of catalyzing photochemical reactions. The reaction chosen was photoreactivation of thymine cyclobutane dimers in DNA by using serotonin as cofactor and light of wavelengths longer than the absorption spectrum of DNA...

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Veröffentlicht in:Proceedings of the National Academy of Sciences - PNAS 2004-01, Vol.101 (1), p.65-69
Hauptverfasser: Daniel J.-F. Chinnapen, Sen, Dipankar
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Sen, Dipankar
description In vitro selection was used to investigate whether nucleic acid enzymes are capable of catalyzing photochemical reactions. The reaction chosen was photoreactivation of thymine cyclobutane dimers in DNA by using serotonin as cofactor and light of wavelengths longer than the absorption spectrum of DNA. Curiously, the dominant single-stranded DNA sequence selected, UV1A, was found to repair its internal thymine dimer substrate efficiently even in the absence of serotonin or any other cofactor. UV1C, a 42-nucleotide fragment of UV1A, repaired the thymine dimer substrate in trans (kcat/kuncat= 2.5 × 104), showing optimal activity with 305 nm light and thus resembling naturally occurring photolyase enzymes. Mechanistic investigation of UV1C indicated that its catalytic role likely exceeded the mere positioning of the substrate in a conformation favorable for photoreactivation. A higher-order structure, likely a quadruplex, formed by specific guanine bases within the deoxyribozyme, was implicated as serving as a light-harvesting antenna, with photoreactivation of the thymine dimer proceeding possibly via electron donation from an excited guanine base. In a primordial "RNA world," self-replicating nucleic acid populations may have been vulnerable to deactivation via UV light-mediated pyrimidine dimer formation. Photolyase nucleic acid enzymes such as the one described here could thus have played a role in preserving the integrity of such an RNA world.
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subjects Absorption spectra
Base Sequence
Biochemistry
Biological Sciences
Deoxyribonucleic acid
deoxyribozymes
Dimers
DNA
DNA Repair
DNA, Catalytic - chemistry
DNA, Catalytic - genetics
DNA, Catalytic - metabolism
Electrons
Enzymes
Kinetics
Light
Models, Biological
Nucleic Acid Conformation
Nucleic acids
Oligonucleotides
Photochemistry
Pyrimidine Dimers - metabolism
Ribonucleic acid
RNA
Sodium
Spectrophotometry
Splints
thymine dimers
Ultraviolet Rays
Wavelengths
title A Deoxyribozyme That Harnesses Light to Repair Thymine Dimers in DNA
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