A Fifth DNA Base?

A ubiquitous but rare DNA base, previously thought to be a transitional chemical modification of cytosine, has now been shown to be stably incorporated in mammalian DNA. 5-formylcytosine (5fC) is found in all tissues, with the highest levels being found in the brain. Its exact function is unknown, but its physical position in the genome suggests that it plays a key role in gene expression.

Scientists at the University of Cambridge and the Babraham Institute used high-resolution mass spectrometry to examine in vivo levels of 5fC in adult and embryonic mouse tissues and in mouse embryonic stem cells. In addition, the researchers fed cells and mice with L-methionine, an essential amino acid containing stable carbon and hydrogen isotopes, and evaluated the 5fC in brain DNA for levels of these isotopes. Low uptake of these stable isotopes suggested that 5fC is a stable modification.

The researchers believe that 5fC can change the shape of the DNA helix and affect the way that DNA interacts with proteins. This could, as a result, alter gene expression, since the modified DNA structure would associate with different proteins than the unmodified DNA. More research is being carried out to determine the function of this new base and to see how it interacts with or relates to the original four better known bases.

Source: University of Cambridge