The discovery, which shows that a process dubbed the DDR (DNA Damage Response) also controls communication from cell to cell, has implications for both cancer and aging. The findings appear in the July 13 online edition of the Nature Cell Biology.
When a cell experiences DNA damage, its first response is to try to repair the damage. If that doesn’t work the cell, hopefully, either commits suicide or stops dividing, two intrinsic mechanisms for preventing cancer according to Judith Campisi, PhD, lead author of the study and a faculty member at the Buck Institute for Age Research. The discovery of the extracellular signaling mechanism, which sets off an inflammatory response, explains how unsuccessful DNA repair at the cellular level impacts tissues, which are the vital units of function in complex organisms like humans, she said.
“With regard to cancer, we found that if there is a mutant and potentially cancerous cell in the vicinity of the damaged cell, the signals from the damaged cell can encourage that mutant cell to behave more aggressively cancerous,” said Campisi. “With regard to aging, we think the inflammatory signals from damaged cells propagate an aging ‘field’ whereby damage builds up over time, impacting not only the individual damaged cells, but the function of the tissue itself.” When Buck scientists disabled particular proteins involved in the DDR, the cell-to-cell communication was cut off.
Buck Institute scientist Francis Rodier, PhD, led the team that did the research in the Campisi lab. He was surprised to find that even though the DDR signaling process was activated inside the cultured human cells within minutes of the DNA damage, it took 24 to 48 hours for the damaged cells to start secreting the inflammatory signals.
“We think the cell is giving itself time to repair its DNA before alerting the immune system that there’s a problem,” said Rodier. He added that scientists were also surprised to discover that the damage-induced communication signaling pathway bypasses a powerful tumor suppressor gene known as p53. That finding gives scientists a target to shut down the inflammatory process without hampering the activity of p53, which is essential to prevent cancer. It also explains why cancerous tumors are still able to secrete inflammatory signals when p53 has mutated and lost its tumor suppressing capabilities. “Inflammation is a hallmark symptom of cancer,” said Rodier. “Inflammation also promotes cancer, so this helps us begin to understand what’s involved in that process.”
The findings also help explain the aging process Campisi said. The immune system, which destroys damaged cells (such as skin cells whose DNA has been exposed to UV radiation), is not perfect, she said. “Damaged cells that survive the activity of the immune system are sending out continuous danger signals to surrounding cells. That constant alarm drives inflammation, which helps drive aging.” Campisi added, “Now we have a target to focus on that could stop those damaged cells from sending out the inflammatory signals.”
Other researchers involved in the study include Jean-Philippe Coppé, Christopher K. Patil, Adam Freund, Denise P. Muñoz and Albert R. Davalos, also of the Buck Institute, along with Eric Campeau, Wieteke A. M. Hoeijmakers, and Saba R. Raza of the Lawrence Berkeley National Laboratory, Berkeley, CA. The work was supported by grants from the National Institutes of Health, a grant from the California Breast Cancer Research Program, a Larry L. Hillblom Foundation fellowship, the Netherlands Organization for International Cooperation in Higher Education, the Dutch Cancer Society, and the Department of Energy under contract to the University of California.About the Buck Institute:
Kris Rebillot | Newswise Science News
Scientists uncover the role of a protein in production & survival of myelin-forming cells
19.07.2018 | Advanced Science Research Center, GC/CUNY
NYSCF researchers develop novel bioengineering technique for personalized bone grafts
18.07.2018 | New York Stem Cell Foundation
For the first time ever, scientists have determined the cosmic origin of highest-energy neutrinos. A research group led by IceCube scientist Elisa Resconi, spokesperson of the Collaborative Research Center SFB1258 at the Technical University of Munich (TUM), provides an important piece of evidence that the particles detected by the IceCube neutrino telescope at the South Pole originate from a galaxy four billion light-years away from Earth.
To rule out other origins with certainty, the team led by neutrino physicist Elisa Resconi from the Technical University of Munich and multi-wavelength...
For the first time a team of researchers have discovered two different phases of magnetic skyrmions in a single material. Physicists of the Technical Universities of Munich and Dresden and the University of Cologne can now better study and understand the properties of these magnetic structures, which are important for both basic research and applications.
Whirlpools are an everyday experience in a bath tub: When the water is drained a circular vortex is formed. Typically, such whirls are rather stable. Similar...
Physicists working with Roland Wester at the University of Innsbruck have investigated if and how chemical reactions can be influenced by targeted vibrational excitation of the reactants. They were able to demonstrate that excitation with a laser beam does not affect the efficiency of a chemical exchange reaction and that the excited molecular group acts only as a spectator in the reaction.
A frequently used reaction in organic chemistry is nucleophilic substitution. It plays, for example, an important role in in the synthesis of new chemical...
Optical spectroscopy allows investigating the energy structure and dynamic properties of complex quantum systems. Researchers from the University of Würzburg present two new approaches of coherent two-dimensional spectroscopy.
"Put an excitation into the system and observe how it evolves." According to physicist Professor Tobias Brixner, this is the credo of optical spectroscopy....
Ultra-short, high-intensity X-ray flashes open the door to the foundations of chemical reactions. Free-electron lasers generate these kinds of pulses, but there is a catch: the pulses vary in duration and energy. An international research team has now presented a solution: Using a ring of 16 detectors and a circularly polarized laser beam, they can determine both factors with attosecond accuracy.
Free-electron lasers (FELs) generate extremely short and intense X-ray flashes. Researchers can use these flashes to resolve structures with diameters on the...
13.07.2018 | Event News
12.07.2018 | Event News
03.07.2018 | Event News
19.07.2018 | Earth Sciences
19.07.2018 | Power and Electrical Engineering
19.07.2018 | Materials Sciences