A deoxyribozyme, Sero1C, uses light and serotonin to repair diverse pyrimidine dimers in DNA.
An in vitro selection search for DNAs capable of catalyzing photochemistry yielded two distinctive deoxyribozymes (DNAzymes) with photolyase activity: UV1C, which repaired thymine dimers within DNA using a UV light of >300 nm wavelength and no extraneous cofactor, and Sero1C, which required the tryptophan metabolite serotonin as cofactor in addition to the UV light. Catalysis by Sero1C conformed to Michaelis-Menten kinetics, and analysis of the action spectrum of Sero1C confirmed that serotonin did indeed serve as a catalytic cofactor rather than as a structural cofactor. Sero1C and UV1C showed strikingly distinct wavelength optima for their respective photoreactivation catalyses. Although the rate enhancements characteristic of the two DNAzymes were similar, the cofactor-requiring Sero1C repaired a substantially broader range of substrates compared to UV1C, including thymine, uracil, and a range of chimeric deoxypyrimidine and ribopyrimidine dimers. Similarities and differences in the properties of these two photolyase DNAzymes suggest, first, that the harnessing of less damaging UV light for the repair of photolesions may have been a primordial catalytic activity of nucleic acids, and, second, the broader substrate range of Sero1C may highlight an evolutionary advantage to coopting amino-acid-like cofactors by functionality-poor nucleic acid enzymes.
Thorne
Rebecca E
RE
Department of Molecular Biology and Biochemistry, Simon Fraser University, Burnaby, British Columbia, Canada V5A 1S6.
Chinnapen
Daniel J-F
DJ
Sekhon
Gurpreet S
GS
Sen
Dipankar
D
D001483:Base Sequence; D004247:DNA / Q000737:chemistry*; D004260:DNA Repair; D021881:DNA, Catalytic / Q000737:chemistry* / Q000378:metabolism; D007700:Kinetics; D008954:Models, Biological; D008969:Molecular Sequence Data; D009690:Nucleic Acid Conformation; D010777:Photochemistry; D011740:Pyrimidine Dimers / Q000737:chemistry* / Q000378:metabolism; D012701:Serotonin / Q000737:chemistry*; D013379:Substrate Specificity
D021881:DNA, Catalytic; D011740:Pyrimidine Dimers; D012701:Serotonin; D004247:DNA