Researchers in Japan have created a molecular padlock that can lock onto sections of DNA and be unlocked on command. The padlock obstructs DNA-cleaving enzymes and could potentially be used to halt gene transcription.

Kenzo Fujimoto from the Japan Advanced Institute of Science and Technology, Ishikawa, and his colleagues made the padlock by connecting two short stretches of single-stranded nucleic acid with an ethylene glycol linker. One of the two stretches had a vinyl-substituted base at one end. Under light of a particular wavelength, the vinyl group binds to the end of the other nucleic acid, producing a circular molecule sporting a specific oligonucleotide sequence.

The team tested the padlock with a DNA target sequence complementary to that of the oligonucleotide. They introduced the sequence into a plasmid - a ring of double-stranded DNA - and added the oligonucleotide, irradiating the mixture with light. The group found that the oligonucleotide bound to the target sequence and that the bound sequence was not cleaved by DNA-cleaving enzymes, although these acted freely elsewhere on the plasmid. The team was also able to convert the padlock back to linear oligonucleotide by irradiation at a different wavelength, freeing the plasmid.

Fujimoto suggested that the technology could also be used to prevent gene transcription. 'Padlock probes can act as inhibitors to block the DNA-protein interaction required for transcriptional initiation,' he said. 'This is not only another tool for photochemists, but also a new development to control gene expression by a photochemical switch.'

Michael Spencelayh