Thursday, December 14, 2006

The News and Views section of the November 30th edition of 'Nature' magazine(pp553-554) contains an interesting article entitled 'A broader take on DNA' that discusses the latest research on synthesis of modified forms of DNA. The article reports on a paper in the Journal of the American Chemical Society (Lynch, S.R., Liu, H, Gao, J and Kool, E.T., J. Am. Chem. Soc. 128, 14704-14711 (2006)) that describes the synthesis of an "expanded" form of DNA that can carry twice the amount of genetic information of normal DNA.
The new form of DNA which the authors have christened "xDNA" is made by modification of the four normal bases of DNA, adenine, guanine, cytosine and thymine, by the addition of an extra benzene ring between the backbone of deoxyribose and the active area of the bases that form hydrogen bonds. The extra rings sit perpendicular to the long axis of the polymer formed by the hydrogen bonds. The reason that this formation carries extra information is that while ordinary DNA has only two possible base pairs, A-T and C-G, xDNA has four possible combinations, xG-C, G-xC, xA-T and A-xT.
This synthetic form of DNA has a few interesting differences from natural DNA. The synthetic form is more stable than natural DNA because of an increase in "stacking" , both within strand and between strands. Also 12 base pairs are required to complete one turn of the helix as opposed to ten in natural DNA. Because of this the major and minor grooves of the helix are broader and shallower than in regular DNA. These grooves determine the interactions of DNA with both proteins and smaller molecules, and therefore xDNA will interact with such molecules in ways different from natural DNA. xDNA is also naturally fluorescent, unlike regular DNA.
There are barriers to the use of xDNA. DNA polymerases do not interact properly with the altered geometry to initiate replication of the altered DNA. While "directed evolution" of polymerases, with in vitro mutation and selection, (shades of intelligent design), has had some success in altering the normal forms of the enzyme it would be a giant step to try and engineer a polymerase that could initiate replication in xDNA.
Yet there is great promise that such synthetic forms of DNA could help elucidate the normal forms of DNA's interactions with other molecules by offering a comparative model.
Til then, Molly has to say that the synthesis of a "Rosie O'Donnell" form of DNA is a remarkable achievement on its own. Plumper and cuter. Undoubtedly Santa's DNA is a naturally occurring form of this molecule.
Merry Christmas,

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