DNA Catalyst Cuts DNA Sequence-Specifically

While searching for a DNA oligonucleotide capable of snipping proteins, Scott K. Silverman and coworkers of the University of Illinois, Urbana-Champaign, serendipitously found one that instead cleaves single-stranded DNA, a much harder task. Without a catalyst, it’s at least 400 times more difficult energetically to hydrolyze a DNA- than an RNA-phosphodiester bond. The researchers report that the DNA catalyst, which requires the presence of two metals, Mn²⁺ and Zn²⁺, cleaves DNA between G and T at 5′-ATGT-3′ recognition sites (Nat. Chem. Biol., DOI: 10.1038/nchembio.201). A self-oxidizing DNA and a self-hydrolyzing G-quadruplex DNA have been reported before, but these cannot cleave a range of sequences. The new catalyst’s hydrolysis mechanism, like that of restriction enzymes, is less destructive than oxidation. And Silverman believes the new catalyst can potentially cleave a broad range of sequences and also be adapted to cleave duplex DNA. “By appropriately picking the recognition and enzyme regions of the catalyst, we should be able to cut many more DNA sequences than is possible with current restriction enzymes,” he said.