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Chemical Biology

A supplement providing a snapshot of the latest developments in chemical biology



Locating DNA modifications


03 April 2006

Researchers could be closer to understanding how embryos develop and how normal cells turn into cancer cells, thanks to a discovery by Japanese scientists.

Akimitsu Okamoto and colleagues from Kyoto University have found a way to distinguish between the normal DNA base cytosine and its methylated counterpart 5-methylcytosine. The modified cytosine is often found in genomic DNA where it regulates gene expression and cell differentiation, though how this works is largely unknown.

DNA strand cleavage

The researchers discovered that an osmium complex oxidises 5-methylcytosine, but leaves regular cytosine alone. A DNA strand pre-treated with the complex can be split specifically at the oxidised sites. If analysis shows that the DNA has split, this means it contained methylated cytosines.

The group were able to use their approach to determine whether a specific site in a DNA sequence was methylated. Pinpointing exactly which cytosines are methylated in a gene could help in understanding how methylation controls cell differentiation, answering such questions as why a healthy cell suddenly turns cancerous, said Okamoto.

"The challenge in DNA methylation is to develop methods that are both high-throughput and quantitative"
- Guoping Fan
The technique is more efficient than current methods, which are hampered by complicated procedures and long reaction times, said Okamoto. He now aims to develop a method to determine how many cytosines in a DNA sequence are methylated and which of these sites are important, for example in gene expression.

Guoping Fan, an expert in the field from the University of California, Los Angeles, US, is interested in Okamoto's discovery. 'The challenge in DNA methylation is to develop methods that are both high-throughput and quantitative,' he said, 'this method has good potential.'

Daničle J Gibney

References

A Okamoto et al, Org. Biomol. Chem., 2006 (DOI: 10.1039/b600401f)