Umeå researchers solve long-standing riddle: Show what enzyme copies genes

The human genome has already been mapped, as have the genomes of several other organisms. On the other hand, little has been known how genes are copied and repaired so efficiently and precisely. These processes always involve a so-called DNA polymerase, an enzyme that performs the actual new growth of genes.

The genes consist of two DNA strands, but scientists have not known what polymerase copies the two DNA strands. It has been known, however, that DNA polymerase epsilon is responsible for a great deal of this synthesis in higher organisms, and that it does so with the greatest precision.

The researchers describe in the article how they mutated DNA polymerase epsilon, creating an enzyme that makes a particular error when it copies genes. This means that the enzyme leaves a signature at all sites where it copies the genes in the cell.

By reading where this signature is left, the scientists have then been able to determine that DNA polymerase epsilon copies one of the strands, the so-called “leading” strand. For decades researchers have been wondering what enzyme synthesizes this particular part, and now proof has been found.

These research findings, which describe fundamental biological functions, pave the way for an enhanced understanding of how mutations occur in genes, mutations that can lead to cancer, for instance.

Contributors from Umeå University are Erik Johansson, a researcher at the Department of Medical Biochemistry and Biophysics, together with doctoral student Isabelle Isoz and laboratory assistant Else-Britt Lundström.

The U.S. authors Zacchary Pursell and Thomas A. Kunkel work at the National Institute of Environmental Health Sciences, NIH.

The article can be read at http://www.sciencemag.org/ and is titled “Yeast DNA polymerase epsilon participates in leading-strand synthesis” Pursell, Z.F., Isoz, I., Lundström, E.-B., Johansson, E., and Kunkel, T.A.

For more information, please contact Erik Johansson, Dept. of Medical Biochemistry and Biophysics, cell phone: +46 (0)73-620 50 61, phone: +46 (0)90-786 6638, e-mail erik.johansson@medchem.umu.se.

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