The structure is published in the January 15 Nature , along with results from a research collaboration led by crystallographer Thomas Ellenberger and biochemist Charles Richardson, assistant professor and professor, respectively, of biological chemistry and molecular pharmacology at Harvard Medical School. Other researchers had previously figured out the crystal structure of related enzymes but had never been able to include all the players necessary for DNA duplication. Moreover, this work for the first time depicts a so-called replicative polymerase. They are slow and make errors frequently. This work shows in exquisite detail how the polymerase recognizes the right nucleotide to be paired to the single-stranded DNA, and thus helps explain how this enzyme achieves its high accuracy of about one mistake per million nucleotides.
Mistakes cause mutations and, in certain genes, can lead to cancer.
The other researchers on this project include lecturer Stanley Tabor, who figured out the biochemical conditions to enable crystallography, postdoctoral fellow Sylvie Doublie, who produced the crystal structure, and Alexander Long, a technician.