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07 May 17:25

Bacteria engineered to copy DNA with synthetic base pairs

by John Timmer
John Timmer

Although the information that can be crammed into a genome is remarkably complex, the molecule underlying it all obeys remarkably simple rules. In every creature we've studied, there are four bases that always pair the same way: A with T, and G with C. These combinations are dictated by basic chemistry. The two pairings form different numbers of hydrogen bonds but keep the spacing between the two strands of DNA constant.

But synthetic chemists haven't been willing to sit still and accept what nature has given them. It's possible to come up with a variety of similarly shaped molecules that can pair up in a way that keeps the spacing of DNA constant but forms base pairs that are physically distinct from those of A, T, C, and G. In many cases, the enzymes that copy DNA don't really care about the precise chemical details; as long as there's a successful base pairing, they'll incorporate it into the DNA.

As a result, biochemists have managed to build DNA and RNA with a variety of synthetic bases and get enzymes to work with them—at least in test tubes. Getting these synthetic bases into a cell and fully incorporated into the processes that keep the cell dividing has been a significantly larger challenge. But now, researchers have reported that they've gotten bacteria to maintain a small piece of DNA that includes these synthetic bases. The work is a bit limited, but it's an important proof-of-principle.

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