A deoxyribozyme that harnesses light to repair thymine dimers in DNA

被引:150
作者
Chinnapen, DJF [1 ]
Sen, D [1 ]
机构
[1] Simon Fraser Univ, Dept Mol Biol & Biochem, Burnaby, BC V5A 1S6, Canada
关键词
D O I
10.1073/pnas.0305943101
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
In vitro selection was used to investigate whether nucleic acid enzymes are capable of catalyzing photochemical reactions. The reaction chosen was photo reactivation 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 he 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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页码:65 / 69
页数:5
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