Towards Elucidation of the Mechanism of UV1C, a Deoxyribozyme with Photolyase Activity
Among the unexpected chemistries that can be catalyzed by nucleic acid enzymes is photochemistry. We have reported the in vitro selection of a small, cofactor-independent deoxyribozyme, UV1C, capable of repairing thymine dimers in a DNA substrate, most optimally with light at a wavelength of >300...
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Veröffentlicht in: | Journal of molecular biology 2007-02, Vol.365 (5), p.1326-1336 |
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description | Among the unexpected chemistries that can be catalyzed by nucleic acid enzymes is photochemistry. We have reported the
in vitro selection of a small, cofactor-independent deoxyribozyme, UV1C, capable of repairing thymine dimers in a DNA substrate, most optimally with light at a wavelength of >300 nm. We hypothesized that a guanine quadruplex functioned both as a light antenna and an electron source for the repair of the substrate within the enzyme–substrate complex. Here, we report structural and mechanistic investigations of that hypothesis. Contact-crosslinking and guanosine to inosine mutational studies reveal that the thymine dimer and the guanine quadruplex are positioned close to each other in the deoxyribozyme–substrate complex, and permit us to refine the structure and topology of the folded deoxyribozyme. In exploring the substrate utilization capabilities of UV1C, we find it to be able to repair uracil dimers as well as thymine dimers, as long as they are present in an overall deoxyribonucleotide milieu. Some surprising similarities with bacterial CPD photolyase enzymes are noted. |
doi_str_mv | 10.1016/j.jmb.2006.10.062 |
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in vitro selection of a small, cofactor-independent deoxyribozyme, UV1C, capable of repairing thymine dimers in a DNA substrate, most optimally with light at a wavelength of >300 nm. We hypothesized that a guanine quadruplex functioned both as a light antenna and an electron source for the repair of the substrate within the enzyme–substrate complex. Here, we report structural and mechanistic investigations of that hypothesis. Contact-crosslinking and guanosine to inosine mutational studies reveal that the thymine dimer and the guanine quadruplex are positioned close to each other in the deoxyribozyme–substrate complex, and permit us to refine the structure and topology of the folded deoxyribozyme. In exploring the substrate utilization capabilities of UV1C, we find it to be able to repair uracil dimers as well as thymine dimers, as long as they are present in an overall deoxyribonucleotide milieu. 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in vitro selection of a small, cofactor-independent deoxyribozyme, UV1C, capable of repairing thymine dimers in a DNA substrate, most optimally with light at a wavelength of >300 nm. We hypothesized that a guanine quadruplex functioned both as a light antenna and an electron source for the repair of the substrate within the enzyme–substrate complex. Here, we report structural and mechanistic investigations of that hypothesis. Contact-crosslinking and guanosine to inosine mutational studies reveal that the thymine dimer and the guanine quadruplex are positioned close to each other in the deoxyribozyme–substrate complex, and permit us to refine the structure and topology of the folded deoxyribozyme. In exploring the substrate utilization capabilities of UV1C, we find it to be able to repair uracil dimers as well as thymine dimers, as long as they are present in an overall deoxyribonucleotide milieu. Some surprising similarities with bacterial CPD photolyase enzymes are noted.</abstract><cop>England</cop><pub>Elsevier Ltd</pub><pmid>17141270</pmid><doi>10.1016/j.jmb.2006.10.062</doi><tpages>11</tpages></addata></record> |
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subjects | Base Sequence Catalysis - drug effects Cross-Linking Reagents - pharmacology Deoxyribodipyrimidine Photo-Lyase - metabolism Deoxyribose - chemistry Deoxyribose - metabolism DNA, Catalytic - metabolism DNAzyme Guanine - metabolism Inosine - genetics Models, Biological Molecular Sequence Data Nucleic Acid Conformation - drug effects photolyase Point Mutation - genetics Pyrimidine Dimers - chemistry Pyrimidine Dimers - metabolism Ribose - chemistry Ribose - metabolism ribozyme RNA - chemistry Substrate Specificity - drug effects thymine dimers |
title | Towards Elucidation of the Mechanism of UV1C, a Deoxyribozyme with Photolyase Activity |
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