Catalytic DNAs That Harness Violet Light To Repair Thymine Dimers in a DNA Substrate

Abstract

UV1C is an <i>in vitro</i> selected catalytic DNA that shows efficient photolyase activity, using light of <310 nm wavelength to photo-reactivate CPD thymine dimers within a substrate DNA. We show here that a minimal mutational strategy of substituting a guanine analogue, 6MI, for single guanine residues within UV1C extends the DNAzyme’s activity into the violet region of the spectrum. These 6MI point mutant DNAzymes fall into three distinct functional classes, which photo-reactivate the thymine dimer along different pathways. Cumulatively, they reveal the <i>modus operandi</i> of the original UV1C DNAzyme to be a surprisingly versatile one. The interchangeable properties of no less than six of the G→6MI point mutants highlight UV1C’s built-in functional flexibility, which may serve as a starting point for the creation of efficient, visible light-harnessing, photolyase DNAzymes for either the prophylaxis or therapy of UV damage to human skin