News in detail

Complex biological systems can be described as a network of chemical processes that take place in molecules. Researchers from the “ChemLife” research initiative at the University of Konstanz are working together in an equally active network comprised of dynamic interconnections - both subject-specific and interdisciplinary. Recent insights into DNA polymerases acquired through interdisciplinary collaboration between researchers in organic chemistry, biochemistry, structural biology and theoretical chemistry show just how productive and mutually inspiring the interaction of biological and chemical expertise can be. These new findings at the molecular level of polymerases can be utilised for genome sequencing and in other areas of molecular biology-based diagnostics. The research results were published on 17 September 2018 in the “Proceedings of the National Academy of Sciences of the United States of America” (PNAS).

The recognition processes of DNA polymerases with modified substrates, which are essential in many biotechnological areas, have been rarely studied at molecular level. As “genome synthesis machines”, these polymerases are responsible for the doubling of DNA during cell division. Professor Andreas Marx, Professor Kay Diederichs and Professor Christine Peter have now jointly succeeded  in obtaining detailed structural insights into polymerases as they interact with modified substrates. This knowledge creates a constructive basis to further explore the topic in its many variants and on a broader scale in the future. For the researchers in Konstanz involved in the “ChemLife” initiative, the practical application and social relevance are both particularly important aspects of their research. Knowledge of how such a modification progresses through a DNA polymerase can be used, for example, to advance genome sequencing: “Many processes in molecular biology diagnostics are based on the use of modified building blocks,” explains Professor Andreas Marx, who is a member of the “ChemLife” initiative at the University of Konstanz.

Numerous collaborative projects, the Konstanz Research School Chemical Biology as well as the two Collaborative Research Centres “Chemical and Biological Principles of Cellular Proteostasis” and “Anisotropic Particles as Building Blocks: Tailoring Shape, Interactions and Structures” are interacting in an extensive and effective way with productive results : The new research findings on DNA polymerase line up alongside the latest article on the structural analysis of the FAT 10 protein by Professor Christine Peter and Professor Markus Goettrup within a collection of over 200 publications that have resulted from collaborative research projects over the last few years. “ChemLife” intends to continue to use this special dynamic in the future in order to develop new systems and materials with optimized properties at the interface between biology, chemistry and computer science.

Key facts:

• Researchers collaborating in the “ChemLife” research initiative in Konstanz have gained new insights into DNA polymerases in their interaction with modified substrates.
• Original publication: Kropp HM, Dürr SL, Peter C, Diederichs K, and Marx A (2018). Snapshots of a modified nucleotide moving through the confines of a DNA polymerase. Proc. Natl. Acad. Sci. USA
• New insights at the molecular level of DNA polymerases can contribute to molecular biology-based diagnostics, for example in genome sequencing.
• “ChemLife”: Molecules in Functional Systems” is one of three proposed Clusters of Excellence at the Univesity of Konstanz that are currently competing in the German Excellence Strategy competition.