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 | EurekAlert!
New Technique Maps Elusive Chemical Markers on Proteins
03.07.2015 | Salk Institute for Biological Studies
New approach to targeted cancer therapy
03.07.2015 | CECAD - Cluster of Excellence at the University of Cologne
Wind turbines could be installed under some of the biggest bridges on the road network to produce electricity. So it is confirmed by calculations carried out by a European researchers team, that have taken a viaduct in the Canary Islands as a reference. This concept could be applied in heavily built-up territories or natural areas with new constructions limitations.
The Juncal Viaduct, in Gran Canaria, has served as a reference for Spanish and British researchers to verify that the wind blowing between the pillars on this...
New technique combines electron microscopy and synchrotron X-rays to track chemical reactions under real operating conditions
A new technique pioneered at the U.S. Department of Energy's Brookhaven National Laboratory reveals atomic-scale changes during catalytic reactions in real...
Think of an object made of iron: An I-beam, a car frame, a nail. Now imagine that half of the iron in that object owes its existence to bacteria living two and a half billion years ago.
Think of an object made of iron: An I-beam, a car frame, a nail. Now imagine that half of the iron in that object owes its existence to bacteria living two and...
A team of scientists including PhD student Friedrich Schuler from the Laboratory of MEMS Applications at the Department of Microsystems Engineering (IMTEK) of...
The three-year clinical trial results of the retinal implant popularly known as the "bionic eye," have proven the long-term efficacy, safety and reliability of...
25.06.2015 | Event News
16.06.2015 | Event News
11.06.2015 | Event News
03.07.2015 | Press release
03.07.2015 | Agricultural and Forestry Science
03.07.2015 | Health and Medicine