After NaM and 5SICS were made, several other groups of researchers found that a natural strand of DNA with NaM and 5SICS added to it will still copy itself nearly as well as all-natural DNA. Scientists didn't know why it worked so well. They worried they had somehow "tricked" the body's DNA copying machine, called DNA polymerase, said Floyd Romesberg, a chemist at the Scripps Research Institute in La Jolla, Calif. Romesberg was one of the principal inventors of NaM and 5SICS and was involved in this new study, published online yesterday (June 3) in the journal Nature Chemical Biology.
The natural base pairs A, C, G and T have specific shapes and line up neatly with each other along their edges when they're inside a DNA helix. Scientists believe their shape and neat fit are important for DNA polymerase to work properly. On the other hand, NaM and 5SICS aren't shaped anything like the natural bases. They don't use the same chemical bonds as natural bases do and they don't line up edge-to-edge. [ Move Over, DNA, and Meet the More Durable XNA ]
With their X-ray crystallography images, Romesberg — along with colleagues in nearby San Diego, Calif., and in Germany — found that while NaM and 5SICS aren't lined up edge-to-edge inside a strand of DNA, they shift so they are in the correct formation for copying when DNA polymerase comes along. "The DNA polymerase apparently induces this unnatural base pair to form a structure that's virtually indistinguishable from that of a natural base pair," said Denis Malyshev, another Scripps Institute chemist in the study. He and his colleagues think that the chemical bonds the artificial bases use are flexible, so they can shift positions easily.
They also found that when the artificial bases slide inside the polymerase, like a sheet of paper placed inside a copying machine, the polymerase undergoes the same chemical interactions as it does when it works with natural bases. They also found the polymerase refuses to pair an artificial base with a natural base, which is similar to how polymerases will only match A's to T's and C's to G's.