Cell aging, or cellular senescence, has an important role in the natural physiological response to tumor development. Activated oncogenes are able to induce senescence, and recent findings have suggested that oncogene-induced senescence (OIS) could play a key role in future cancer therapy. Researchers have now identified a previously unknown mechanism in the regulation of OIS. This study is published online in advance of the January issue of The American Journal of Pathology.
In many types of normal cells, OIS depends on induction of DNA damage response. Oxidative stress and hyper-replication of genomic DNA have already been proposed as major causes of DNA damage in OIS cells. A group of investigators from New York, Oregon, and Michigan reports that down-regulation of deoxyribonucleoside pools is another endogenous source of DNA damage. In normal human cells, "OIS represents an important fail-safe mechanism that suppresses proliferation of pre-malignant cells," explains lead investigator Dr Mikhail Nikiforov, PhD, Department of Cell Stress Biology, Roswell Park Cancer Institute, Buffalo, New York. "Compelling evidence suggests that one of the intrinsic processes required for the induction of OIS is the cellular response to DNA damage."
The group investigated endogenous processes that caused DNA damage in human fibroblasts undergoing OIS and demonstrated that DNA damage, at least partially, originates from under-expression of key enzymes involved in deoxyribonucleoside biosynthesis and subsequent depletion of endogenous deoxyribonucleoside triphosphate (dNTP) pools. They found that even partial restoration of depleted intracellular dNTP pools is sufficient for substantial suppression of DNA damage and senescence.
"We believe our data identify a previously unknown role of deoxyribonucleotides in regulation of oncogene-induced senescence. Our results suggest that both nucleotide depletion and active DNA replication are required for efficient induction of DNA damage and OIS," he concludes.
David Sampson | Source: EurekAlert!
Further information: www.elsevier.com
More articles from Life Sciences:
New genetic research finds shark, human proteins stunningly similar
06.12.2013 | Cornell University
Prostate cancer biomarker may predict patient outcomes
06.12.2013 | Vanderbilt University Medical Center
International team of scientists develops new feedback method for optimizing the laser pulse shapes used in the control of chemical reactions
In many ways, traditional chemical synthesis is similar to cooking. To alter the final product, you can change the ingredients or their ratio, change the method of mixing ingredients, or change the temperature or pressure of the environment of the ingredients.
Like an accomplished chef, chemists have become very skilled ...
A genetic defect protects mice from infection with influenza viruses
A new study published in the scientific journal PLOS Pathogens points out that mice lacking a protein called Tmprss2 are no longer affected by certain flu viruses.
The discovery was made by researchers from the Helmholtz Centre for Infection Research (HZI) in Braunschweig in collaboration with colleagues from Göttingen and ...
The Light: Global study gets underway with online user survey
Light has a fundamental impact on our sense of well-being and performance. In cooperation with Zumtobel, a supplier of lighting solutions, Fraunhofer IAO has launched a global user survey of lighting quality in offices. The objective is to identify the best lighting conditions for a variety of spaces and lighting ...
Quantum entanglement, a perplexing phenomenon of quantum mechanics that Albert Einstein once referred to as “spooky action at a distance,” could be even spookier than Einstein perceived.
Physicists at the University of Washington and Stony Brook University in New York believe the phenomenon might be intrinsically linked with wormholes, hypothetical features of space-time that in popular science fiction can provide a much-faster-than-light shortcut from one part of the universe to another.
But here’s the catch: One couldn’t actually ...
A star is formed when a large cloud of gas and dust condenses and eventually becomes so dense that it collapses into a ball of gas, where the pressure heats the matter, creating a glowing gas ball – a star is born.
New research from the Niels Bohr Institute, among others, shows that a young, newly formed star in the Milky Way had such an explosive growth, that it was initially about 100 times brighter than it is now. The results are published in the scientific journal, Astrophysical Journal Letters.
The young ...
06.12.2013 | Materials Sciences
06.12.2013 | Life Sciences
06.12.2013 | Life Sciences
05.12.2013 | Event News
04.12.2013 | Event News
12.11.2013 | Event News