MYC genes and their proteins play a central role in the onset and development of almost all cancers. They promote the uncontrolled growth and altered metabolism of tumor cells. And they help tumors hide from the immune system.
MYC proteins also show a previously unknown activity that is now opening new doors for cancer research: they form hollow spheres that protect particularly sensitive parts of the genome. If these MYC spheres are destroyed, the cancer cells will die.
This was reported by a research team led by Martin Eilers and Elmar Wolf from the Institute of Biochemistry and Molecular Biology at the Julius-Maximilians-Universität Würzburg (JMU, Bavaria, Germany) in the journal “Nature”. The researchers are convinced that their discovery is a game changer for cancer research, an important breakthrough on the way to new therapeutic strategies.
Hollow spheres protect sensitive DNA sites
What the researchers discovered: When laboratory cells are kept under stressful conditions similar to those found in fast-growing tumor cells, the MYC proteins in the cell nucleus rearrange in a way spectacular They come together to form hollow spheres made up of thousands of MYC proteins.
The hollow spheres surround and protect individual, particularly sensitive sites in the genome, precisely the places where two types of enzymes can collide: enzymes that read DNA to synthesize RNA and enzymes that duplicate DNA. Both can be thought of as two trains traveling on a single track, in DNA.
Thus, the hollow spheres prevent the two enzymes from colliding. The Würzburg team was able to confirm this observation in cancer cells. If the protective function of the protein spheres is experimentally disabled, the enzymes collide and, as a consequence, multiple breaks occur in the DNA, which ultimately kill the cancer cells.
Search for specifically effective drugs
These observations revolutionize our understanding of why MYC proteins are so crucial for tumor cell growth.”
Martin Eilers, Institute of Biochemistry and Molecular Biology of the Julius-Maximilians-Universität Würzburg
The new findings also raise the question of whether drugs can be developed that specifically prevent the formation of hollow spheres.
To drive this development, Eilers and Wolf have created a company. Together with JMU and partners in the pharmaceutical industry, the search for drugs that interfere with the newly discovered functions of MYC proteins has begun.
“The fact that investors have made it possible for us to set up so quickly is certainly not an everyday occurrence,” the JMU professors say. They also take this as a sign that they have made a very promising discovery.
Source:
Journal reference:
Eilers, M., et al. (2022) Multimerization of MYC shields stalled RNA polymerase replication forks. Nature. doi.org/10.1038/s41586-022-05469-4.