A deoxyribozyme that harnesses light to repair thymine dimers in DNA.
نویسندگان
چکیده
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 (k(cat)/k(uncat) = 2.5 x 10(4)), 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.
منابع مشابه
Serologic estimation of thymine dimers in the deoxyribonucleic acid of bacterial and mammalian cells following irradiation with ultraviolet light and postirradiation repair.
The repair of thymine dimers induced by irradiation with ultraviolet light was detected in the DNA of human fibroblast cells, HeLa, but not in the DNA of rat glial or rat pituitary cells. Thymine dimers were detected in the DNA of bacterial and mammalian cells after irradiation with levels of light which are biologically significant, as little as 50 ergs per mmz. The detection of thymine dimers...
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عنوان ژورنال:
- Proceedings of the National Academy of Sciences of the United States of America
دوره 101 1 شماره
صفحات -
تاریخ انتشار 2004