MYC genes and their proteins play a central role in the emergence and development of almost all cancers. They drive the uncontrolled growth and altered metabolism of tumor cells. And they help tumors hide from the immune system.
MYC proteins also show an activity that was previously unknown – and which 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, cancer cells will die.
This was reported by a research team 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.
What the researchers discovered: When cells in the lab are kept under stress conditions similar to those found in fast-growing tumor cells, the MYC proteins in the cell nucleus rearrange themselves in a dramatic way. They join together to form hollow spheres consisting of thousands of MYC proteins.
The hollow spheres surround and protect individual, particularly sensitive sites in the genome – precisely the sites 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 travelling on only one track, on DNA.
The hollow spheres thus prevent the two enzymes from colliding. The team was able to confirm this observation in cancer cells. If the protective function of the protein spheres is switched off experimentally, collisions of the enzymes occur and, as a consequence, multiple breaks occur in the DNA – which ultimately kill the cancer cells.
"These observations revolutionize our understanding of why MYC proteins are so crucial for the growth of tumor cells," says the author. The new findings also raise the question of whether drugs can be developed that specifically prevent the formation of the hollow spheres.
MYC multimers shield stalled replication forks from RNA polymerase
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