The importance of nucleotide size in the chemistry and biology of DNA

Published on August 14, 2008 Updated on December 22, 2020   41 min

A selection of talks on Biochemistry

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0:00
The title of this talk is the importance of nucleotide size in the chemistry and biology of DNA. I'm Eric Kool, I'm in the chemistry department at Stanford University.
0:12
In this talk, I'll discuss experiments we've carried out in which we change the size of DNA bases. Now, why do we do this? Three main reasons. First, is to find out how flexible and adaptable the DNA backbone is. Second, is to find out how proteins that recognize DNA depend on the sizes and shapes of DNA bases. Third, is the design strategy that we'd like to understand how flexible the DNA is in order to design possible new genetic systems.
0:44
During the talk, I'll discuss two design strategies used in our laboratory, the use of benzo-expanded DNA bases; these have Watson-Crick hydrogen bonding groups. The second strategy is the use of incrementally expanded DNA bases; these are non-polar molecules that lack hydrogen bonding groups. We take two different strategies to approach this problem of the effects of DNA size from two directions.
1:11
In the first part of the talk, I'll discuss our benzo-expansion strategy for designed DNA bases. This will involve two sets of molecules, the first called xDNA and the more recent set called yDNA.
1:26
In our xDNA or expanded DNA project, we have several long-term goals. First, is to replace all of the DNA base pairs with ones of our own design. Second, is to see if these molecules can possess DNA-like functions, the natural biological functions, for example, DNA replication. Third, we hope that there are some applications that may be useful for these molecules, including detection of nucleic acids and possible imaging of nucleic acids inside cells. The reasons we think this work is important are two-fold. First, we're asking if other genetic systems, other molecular designs could exist in function. In part, this is a human question that is, can a person design such a molecule? Second, it's a biological question; how did our DNA evolve and could other structures have evolved? The second important reason we think for doing this is that we believe that there are possible applications to design genetic systems.

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