Seventh and Eighth Bases of DNA Discovered

The seventh and eighth bases of DNA has been discovered by scientists.

These last two bases, called 5-formylcytosine and 5 carboxylcytosine, are actually versions of cytosine that have been modified by Tet proteins, molecular entities thought to play a role in DNA demethylation and stem cell reprogramming.Thus, the discovery could advance stem cell research by giving a glimpse into the DNA changes, such as the removal of chemical groups through demethylation, which could reprogram adult cells to make them act like stem cells. "Before we can grasp the magnitude of this discovery, we have to figure out the function of these new bases," senior study author Yi Zhang, Ph.D., Kenan Distinguished Professor of biochemistry and biophysics at UNC and an Investigator of the Howard Hughes Medical Institute, said.

"Because these bases represent an intermediate state in the demethylation process, they could be important for cell fate reprogramming and cancer, both of which involve DNA demethylation," Zhang explained.

Last year, Zhang's group reported that Tet proteins can convert 5 methylC (the fifth base) to 5 hydroxymethylC (the sixth base) in the first of a four step reaction leading back to bare-boned cytosine.

But try as they might, the researchers could not continue the reaction on to the seventh and eighth bases, called 5 formylC and 5 carboxyC.
The problem, they eventually found, was not that Tet wasn't taking that second and third step, it was that their experimental assay wasn't sensitive enough to detect it.