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Uncovering DNA's 'sweet' secret

DNA's simple and elegant structure - the "twisted ladder," with sugar-phosphate chains making up the "rails" and oxygen- and nitrogen-containing chemical "rungs" tenuously uniting the two halves - seems to be the work of an accomplished sculptor.

Yet the graceful, sinuous profile of the DNA double helix is the result of random chemical reactions in a simmering, primordial stew.

Just how nature arrived at this molecule and its sister molecule, RNA,remains one of the greatest - and potentially unsolvable - scientific mysteries.

But Vanderbilt biochemist Martin Egli, Ph.D., isn't content to simplystudy these molecules as they are. He wants to know why they are the way they are.

"These molecules are the result of evolution," said Egli, professor of Biochemistry. "Somehow they have been shaped and optimized for aparticular purpose."

"For a chemist, it makes sense to analyze the origin of these molecules."

One particular curiosity: how did DNA and RNA come to incorporate five-carbon sugars into their "backbone" when six-carbon sugars, like glucose, may have been more common? Egli has been searching for the answer to that question for the past 13 years.

Recently, Egli and colleagues solved a structure that divulges DNA's "sweet" secret. In a recent issue of the Journal of the American Chemical Society, Egli and colleagues report the X-ray crystal structure of homo-DNA, an artificial analog of DNA in which the usual five-carbon sugar has been replaced with a six-carbon sugar.

By exchanging the sugars that make up the DNA backbone, researchers can make and test plausible "alternatives" to DNA - alternatives that nature may have tried out before arriving at the final structure. These alternative structures can then reveal why DNA's genetic system is more favorable than the other possible forms.

"If you can change the molecules chemically or functionally, you can see what is so particular about the
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Source:Vanderbilt University Medical Center


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