Howard Hughes Medical Institute is reporting that an international team of researchers has developed a new technique to manipulate and modify specific sequences within a DNA molecule, using DNA methyltransferases, enzymes that are responsible for turning genes on and off:
Methyltransferases require a source for the methyl groups that they attach to DNA, and most often that source is a molecule called S-Adenosyl-L-methionine (AdoMet), sometimes known as SAM or SAMe. Methyltransferases grab the methyl group from AdoMet and transfer it directly to DNA, positioning it with enviable specificity within the sequence. This specificity suggests that the enzymes can be a useful tool in the laboratory. But Klimasauskas [Saulius Klimasauskas, a research scholar at the Institute of Biotechnology in Vilnius, Lithuania -ed.] and colleagues wanted the flexibility to attach more than just a simple methyl group…
To try out their technique, the scientists synthesized molecules that mimicked AdoMet, but had chemical groups with longer carbon chains in the position where the methyl group was usually located. The enzymes were able to grab the bulkier group and transfer it to DNA. Since the family of DNA methyltransferases includes enzymes capable of recognizing more than 200 distinct sequences, this new approach provided an unprecedented ability to manipulate DNA experimentally.
To demonstrate the technique’s potential to alter DNA function, the researchers modified DNA in a position that blocked another enzyme’s ability to snip the molecule at its target site. “No one has really thought about possible applications [of this] before because no one thought it was possible,” said Klimasauskas. He predicts that DNA methyltranferases will become a standard laboratory tool like restriction endonucleases.
Picture caption: “Simulated model of the HhaI methyltransferase (shown as grey van der Waals surface) in ternary complex with the bound synthetic cofactor (spacefill CPK) and its target site (shown in magenta, flipped out target base shown in green) in DNA (grey). Left, a modified target site on DNA is shown that contains the covalently attached extended group (spacefill CPK).”
The Howard Hughes Medical Institute reports…