Singaporean scientists have discovered a new type of catalytic DNA that can cut itself in two.

Tianhu Li and co-workers from the National University of Singapore have observed DNA perform hydrolytic self-cleavage at a specific site. The researchers found that structures called G-quadruplexes are core to these catalytic DNA molecules - DNAzymes - and the results could have important implications in understanding G-quadruplex function in vivo.

The DNA folds into a G-quadruplex and cleaves itself in two

Found in nucleic acids, G-quadruplexes are stacks of two or more square planar arrays of guanine bases. They are thought to exist in a number of important regions of DNA in vivo, including those linked to defence against disease and to aging. The structures have attracted attention from scientists for their unusual spatial arrangement and many thousands of potential quadruplex formation sites have been identified in the human genome. But, while they appear to help control gene activity, their biological function is not yet completely understood.

Now, in a serendipitous discovery, Li and co-workers have shown that DNA containing certain G-quadruplexes can self-cleave in vitro. The team stumbled onto this self-cleavage accidentally when attempting to design a transesterification reaction in a guanine-rich oligonucleotide. 

'The discovery of self-cleavage activity in a short DNA molecule is a landmark finding made all the more interesting by the fact that it is mediated through a G-quadruplex motif,' said Jerry Davies, an expert on nucleic acid structure and function from Queen's University Belfast, UK. 'G-quadruplexes can adopt a wide variety of folding topologies and this raises the possibility that some may catalyse biologically important DNA cleavage reactions in vivo,' he said.

Li explained that this was a possibility, but added: 'We might need to further study whether this type of hydrolytic self-cleavage of DNA could be used by certain DNA-related cellular and viral processes in vivo.' The team said that it hopes the findings will inspire others to further explore the chemical and biological properties of G-quadruplexes.

Freya Mearns