A research team led by Professor Anja Groth at the University of Copenhagen has long been worried about the lack of knowledge related to the basic molecular mechanisms that are responsible for the development and maintenance of the more than 200 specific cell types in the human body. New results have finally caused the team to take out a patent on their latest knowledge.
Science has known for quite some time how a cellular DNA repair protein is directed to lesions in DNA through modifications on histone proteins that are bound tightly to DNA. Cancer cells divide very quickly and experience a high load of damage to DNA. Without quick and efficient repair systems, these cells will inevitably die. Cancer cells are extremely dependent on DNA repair mechanisms and the new molecular mechanism the team found works as a very attractive target for cancer therapy.
The research group from BRIC worked closely with Dinshaw Patel at Memorial Sloan-Kettering Cancer Center in New York. The team located a detailed crystal structure of the TONSL protein bound to the histone protein, which they show is what directs TONSL to lesions on the DNA. This single structure communicates to researchers exactly how the protein works and allows them a wonderful opportunity to design a molecule that can bind to TONSL and stop it from locating the DNA that has been damaged. An inhibitor molecule such as this one may be used in cancer treatment because blocking TONSL function may be able to help promote cancer cells to accumulate DNA damage and eventually die off. The team of researchers has put together a team of experts in medicinal chemistry and rational drug design to develop small molecule inhibitors.
Giulia Saredi, a PhD student has been placed in charge of the functional cell biological experiments. She says that when our cells divide, not only our DNA is copied but also so-called epigenetic information which is vital for the cells to maintain their identity and remain healthy. The epigenetic information is found in a structure known as the chromatin. We have discovered that the TONSL molecule recognizes a special chromatin signature which comes about when the DNA is duplicated during cell division. TONSL is able to read this signature to quicken the speed of repair to damage that has been caused to various portions of our DNA.
Such discoveries made by researchers provide a new foundation to understanding exactly how chromatin (which is the structure that organizes DNA in the nucleus) is able to direct DNA repair processes within our cells. Researchers are currently looking to figure out how our cells function and this has now generated a unique possibility for designing inhibitors that may be useful in the treatment of cancer.
Professor Ana Groth says basic research is our core competence and this discovery shows, once again, that society’s investment in understanding basic biological processes is vital to open new avenues that can be explored for disease treatment. The possibility of exploiting our basic research findings for advancing cancer treatment in the future is an important driving force in our work.
The full study was published in Nature journal.