Combining chemistry with biotechnology, Saulius Klimasauskas, a Howard Hughes Medical Institute (HHMI) international research scholar at the Institute of Biotechnology in Vilnius, Lithuania, and chemists at the Institute of Organic Chemistry in Aachen, Germany, have harnessed a group of essential enzymes to add various chemical groups to DNA, thereby altering its function. The work was published in an early online publication on November 27, 2005 in Nature Chemical Biology.
The enzymes at the heart of the study, known as DNA methyltransferases, are one of the tools cells use to turn genes on and off. By adding a simple cluster of four atoms -- a carbon atom attached to three hydrogens, known to chemists as a methyl group -- to specific bases within a DNA sequence, methyltransferases can effectively shut a gene off. Methylation plays an important role in embryonic development, genomic imprinting, and carcinogenesis because it regulates gene expression.
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 and colleagues wanted the flexibility to attach more than just a simple methyl group.
In this study, the scientists demonstrated that methyltransferases can indeed be used to transfer larger chemical groups to lar
Contact: Jennifer Donovan
Howard Hughes Medical Institute