A nano view of DNA repair
Press release of the Technical University Darmstadt on 16.06.2017
Cells use sophisticated repair mechanisms to deal with damaged genetic material. In cooperation with scientists from Munich and Berlin, researchers from Technische Universität Darmstadt (TU Darmstadt) and GSI Helmholtzzentrum für Schwerionenforschung, Darmstadt, recently identified one of the elementary structural units of this repair mechanism. They reported their findings in the renowned scientific journal Nature Communications.
Genetic material can be damaged during DNA replication and as a result of X-rays and other influences. In most cases, a cell’s DNA repair mechanism responds to damage quickly and effectively. “The spatial organization of the genetic information in the cell nucleus plays a key role in repairing damage,” says M. Cristina Cardoso, Professor of Cell Biology and Epigenetics at the Department of Biology of TU Darmstadt. In the cell nucleus, the thread-like DNA double helixes are clustered closely together with proteins. Areas containing active genes are rather loosely structured, while inactive genetic material is densely packed.
To conduct the studies that the team headed by Cardoso has now published in Nature Communications, the researchers subjected human cells to X-rays in order to induce DNA double-strand breaks. Such breaks are among the most dramatic DNA defects, as they can cause cancer and other severe illnesses.
One of the first steps of the cellular repair process is the phosphorylation of a protein that is involved in the packing of DNA in the cell nucleus. Using super-resolution optical microscopy, the researchers discovered clusters composed of phosphorylated proteins and subunits of DNA clusters. These clusters, which measure only a few hundred nanometers, form tiny units, each one capable of the repair of a DNA double-strand break. When the scientists analyzed the temporal distribution of the clusters in cell nuclei, they noticed that loosely packed DNA is repaired faster than densely packed DNA. Repairs can be made more easily if the clusters of DNA strands are loosened.
The researchers also found out that the protein CTCF, which controls the spatial distribution of the DNA in the cell nucleus, plays a key role in the repair mechanism. Cells with a low CTCF content are bad at making repairs. CTCF probably stabilizes the genetic material in a form that enables it to be easily repaired.
Although the DNA in a cell nucleus may seem to be a chaotic cluster, it is actually governed by sophisticated packing and unpacking mechanisms. “It’s surprising that we fully understand the molecular structure of DNA, but don’t know very much about its spatial organization inside the cell nucleus,” says Cardoso. That’s why the current study examines not only DNA repair but also the fundamental questions regarding the arrangement of the genetic material within cell nuclei. In this way the research highlights a previously underestimated factor that has a big impact on our health.
In addition to scientists from TU Darmstadt, researchers from Ludwig-Maximilians-Universität München, the Max Delbrück Center for Molecular Medicine, Berlin, and GSI Helmholtzzentrum für Schwerionenforschung, Darmstadt were involved in the study.