The DNA double helix’s sequence is programmed with the genetic information of every cell. When a double DNA strand breaks, it poses a threat to the cells and, if the break is not correctly repaired, it can lead to cancer. Double strand breaks can be caused by exposure to radiation. When a cell is damaged in this way, it has to decide whether the break can be fixed, or whether it should be removed before it causes cancer. If the decision is made for removal, the cell is killed off by a cellular suicide program called “apoptosis”.

Björn Schumacher, one of the senior authors of a recent research paper, explains that two different mechanisms start within seconds after cell damage has occurred. On the one side, the cell starts preparing for apoptosis, but at the same time, it starts repairing itself. The research team have managed to identify a mechanism that assimilates signals from both the cell death mechanism and the ongoing repair process. The process is controlled by a protein called UFD-2. It forms large complexes at the damage site and decides whether it’s time to die, or to proceed with the repair. While this decision-making is taking place, UFD-2 is a connection point that both gives and receives signals.

The nematode Caenorhabditis elegans was used for the experiments performed. Leena Ackermann, lead author of the study, notes that different strains of C. elegans, including genetically modified and wild ones, were used for the study. They were examined after double strand breaks had been induced by exposure to ionizing radiation.

Schumacher believes that the results of the study are important so that scientists can fully understand how and why a cell decides to die or repair. One important finding of the study is that cells that do not have UFD-2 do not undergo apoptosis. Such a condition could lead to a higher risk of a broken cell becoming a cancer cell in humans.

The results of the study could be very relevant to better understanding how DNA damage leads to cancer, as all the proteins that take part in this process are present in humans. The aging process is also driven by DNA damage. Excessive apoptosis can lead to aging and tissue degeneration, although it could also protect us from cancer. UFD-2 was originally identified as a key regulator of protein deprivation by the senior author, Thorsten Hoppe. In this study, UFD-2 forms the controlling centers that synchronize cell death and DNA repair. Hoppe is hopeful that the study results will lead to advances in tumor therapy. He notes that the knowledge gained from this study should provide new pharmaceutical perspectives for fighting cancer. The well-balanced process of protein degradation and apoptosis might be manipulated in future to improve the efficiency of tumor cell clearance.

Study has been published in the Nature Structural & Molecular Biology.

Save

Save