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Biotechnology's newest chemical tool

to 5 units, we provide proof of principle that further extensions should also be tolerated," Klimasauskas said.

Due to their sequence-specific nature, the scientists found that methyltransferases have a distinct advantage over other commonly used labeling techniques for DNA and other biopolymers. "Our approach allows labeling of large native DNA molecules at specific internal or terminal loci," Klimasauskas explained.

While potential applications are many, the researchers next plan to synthesize new AdoMet analogs to expand the collection of chemical groups that can be transferred to DNA by methyltrasferases. Klimasauskas's group is currently working to append useful functional groups to extended chains. For example, researchers often label cellular components with a molecule called biotin, because it binds tightly to another molecule, streptavidin, and thus streptavadin can be used to retrieve the molecule of interest. If biotin were built into an AdoMet analog, Klimasauskas said, it could then be used as a molecular hook to fish out all molecules that would naturally be methylated in the cell. "There is no comparable way for global analysis of the methylation targets in the cell," Klimasauskas observed.

DNA is not the only molecule that is naturally methylated in the cell -- RNA and proteins also undergo methylation, and the enzymes that carry out these reactions also rely on AdoMet as their methyl source. Since the chemistry is the same, this technique is likely to be applicable to those biomolecules as well, further expanding its utility. Klimasauskas said that one potential application might be to label various sites in the ribosome -- the RNA-based site of protein production -- with bright fluorophores using appropriate RNA methyltransferases, enabling real-time dynamic studies of the complicated mechanism of protein translation.


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Source:Howard Hughes Medical Institute


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