Chemists in Japan are a step closer to repairing damaged DNA inside living cells.

Kenzo Fujimoto at the Japan Advanced Institute of Science and Technology and colleagues have developed a technique to target DNA bases. Using their method the researchers can mutate a cytosine base into uracil at a specific site on the DNA backbone. The method is so precise, said Fujimoto, it can select between two cytosine bases adjacent on the DNA strand. 

Fujimoto's method uses a strand of synthetic DNA fitted with a photoreactive end group. The synthetic DNA has a sequence complementary to the DNA targeted for mutation so that the two strands bind together when mixed. UV light triggers a reaction between the photoreactive group and the targeted cytosine and heating converts the tagged cytosine into uracil. The researchers release the selectively mutated DNA using UV irradiation at a different wavelength to break the two strands apart.

Although the protocol is currently limited to cytosine, it uses only simple procedures to trigger the mutation, said Fujimoto. Unlike most existing methods the technique does not involve enzymes, and the highly active photoreactive groups mean further UV-active compounds are not needed to bring about the reaction. Because these extra additives are not required, the method could be developed for medical applications, said Fujimoto. For example, 'the site-specific photochemical DNA manipulation would be used as a tool for photochemical repair [of] damaged DNA.'

Fujimoto's work has been welcomed by Jerry Davies, an expert in DNA structure and function at Queen's University, Belfast. 'While the method does not lend itself directly to introducing site-specific changes at bases other than cytosine, it does provide a successful model that should stimulate further research towards this end,' said Davies.

James Mitchell Crow