DREAM complex could hold key to fighting cancer and living longer
DNA may be the stuff of life, but if it isn't repaired in our bodies on a regular basis, it can lead to diseases that can cause some pretty unpleasant types of death. DNA damage has been linked to the formation of cancer, Alzheimer's disease, COPD and many other serious and often life-threatening conditions. It has also been implicated in our natural aging process. Now researchers may have found a key to why DNA is repaired in certain cells but not in others: a set of proteins called the DREAM complex. The findings may have implications for warding off cancer and extending life, although more research is needed.
The strands of DNA in our bodies are constantly being damaged through the stress of everyday living. For the most part, the damage is repaired by natural biological systems and, if we're lucky, we don't see much of an impact from the breakdown and repair process – except, of course, the cumulative physical degradation that comes from aging.
However, in the case of germ cells, which are egg and sperm precursor cells, DNA damage is normally much less than what is seen in adult cells. The thinking is that because germ cells are responsible for transmitting genetic material from parents to children, evolution has seen to it that damage to the DNA in these critical information carriers is kept to a minimum.
In an effort to find out why this difference between germ cells and mature body cells exists, a research team at the University of Cologne found out that the more developed cells have a group of proteins in them called the DREAM complex (dimerization partner [DP], retinoblastoma [RB]-like, E2F and MuvB), while germ cells do not.
In previous research, the DREAM complex has been linked to gene expression, as well as cancer formation. Postulating that the presence of this complex might somehow inhibit DNA repair in body cells, the researchers ran experiments using a nematode called C. elegans, which is more commonly known as a roundworm.
The study confirmed the theory, and the scientists found that the presence of the DREAM complex did, in fact, limit how many DNA repair mechanisms existed in the nematode cells. "The complex attaches to the DNA’s construction plans containing instructions for the repair mechanisms," says a summary of the research. "This prevents them from being produced in large quantities."
In an additional phase of the study, the team saw success in mice that were genetically predisposed to premature aging. By inhibiting the DREAM complex, the researchers were able to reverse natural damage to DNA in the animals' retinas, which in turn preserved their vision.
Going one step further, the team found that inhibiting the DREAM complex in human cells in the lab with chemical means also boosted their DNA repair functionality. "We were very pleased to see the same effect as we did in C. elegans," said Arturo Bujarrabal, lead author of the study. "The human cells were much more resilient towards DNA damage after treatment."
The team says more research will be needed, but add that the discovery of how the DREAM complex keeps cells from repairing their DNA could open the door to slowing down the ravages of aging and fighting off a range of diseases – including radiation damage from space travel.
"Our findings for the first time allow us to improve DNA repair in body cells and to target the causes of aging and cancer development," said Prof. Björn Schumacher, Director of the Institute for Genome Stability in Aging and Disease at the University of Cologne’s CECAD Cluster of Excellence in Aging Research.
Schumacher was a co-author on the study which has been published in the peer-reviewed journal, Nature Structural & Molecular Biology.
Source: University of Cologne