The insights, reported online the week of Sept. 30, 2013, in the journal Proceedings of the National Academy of Sciences, build on earlier work by the research team and identify new prospects for developing cancer therapies.
The researchers have focused on a complex series of events that cells routinely undertake to repair DNA damaged by sun exposure, smoking and even normal metabolism. If not correctly repaired, DNA breakages can result in cellular damage leading to cancer.
"We never had good assays to measure how DNA breaks are repaired, and there were few good tools to study how that repair unfolds at the molecular level," said senior author Michael Kastan, M.D., PhD, executive director of the Duke Cancer Institute. "Our work for the first time enables us to both sensitively measure the repair of DNA breaks and study the molecular mechanisms by which they occur."
DNA inside the cell faces a challenge for repairing itself because it is so compacted in the cell nucleus. Tightly wrapped in a complex of proteins called chromatin, the DNA is spooled like thread around a protein structure called a nucleosome. DNA could suffer a breakage that would go unheeded if it remained deep within the reel.
The system developed by Kastan and colleagues induced DNA breakage at defined points on the DNA strands, enabling researchers to chronicle events as the cells launched the repair process.
What they described for the first time was a choreographed interaction in which the tightly wound DNA was temporarily loosened when a key protein, called nucleolin, was recruited to the breakage site, disrupting the nucleosome spool. The process was then reversed when the nucleosome was re-formed after repair was complete.
"Our study demonstrates for the first time the functional importance of nucleosome disruption in DNA repair," Kastan said. "This nucleosome disruption allows DNA repair proteins to access the DNA lesion and begin the process of mending the breakage."
Kastan said the finding provides key insights for how cells remain healthy, as well as how the repair process could potentially be manipulated. New cancer therapies, for instance, could target nucleolin to enhance sensitivity of tumor cells to radiation or chemotherapies, he said.
"This could give us an opportunity to make current treatments more potent," Kastan said. "That would be a next area of research, which we are especially interested in pursuing."
In addition to Kastan, study authors included Michael Goldstein, Frederick A. Derheimer and Jacqueline Tait-Mulder; all authors were previously at St. Jude Children's Research Hospital.
The work was supported by grants from the National Institutes of Health (CA71387, CA159826, P30CA14236, and P30CA21765), DFG (German Research Foundation), and the American Lebanese Syrian Associated Charities of St. Jude Children's Research Hospital.
Sarah Avery | EurekAlert!
‘Farming’ bacteria to boost growth in the oceans
24.10.2016 | Max-Planck-Institut für marine Mikrobiologie
Calcium Induces Chronic Lung Infections
24.10.2016 | Universität Basel
Terahertz excitation of selected crystal vibrations leads to an effective magnetic field that drives coherent spin motion
Controlling functional properties by light is one of the grand goals in modern condensed matter physics and materials science. A new study now demonstrates how...
Researchers from the Institute for Quantum Computing (IQC) at the University of Waterloo led the development of a new extensible wiring technique capable of controlling superconducting quantum bits, representing a significant step towards to the realization of a scalable quantum computer.
"The quantum socket is a wiring method that uses three-dimensional wires based on spring-loaded pins to address individual qubits," said Jeremy Béjanin, a PhD...
In a paper in Scientific Reports, a research team at Worcester Polytechnic Institute describes a novel light-activated phenomenon that could become the basis for applications as diverse as microscopic robotic grippers and more efficient solar cells.
A research team at Worcester Polytechnic Institute (WPI) has developed a revolutionary, light-activated semiconductor nanocomposite material that can be used...
By forcefully embedding two silicon atoms in a diamond matrix, Sandia researchers have demonstrated for the first time on a single chip all the components needed to create a quantum bridge to link quantum computers together.
"People have already built small quantum computers," says Sandia researcher Ryan Camacho. "Maybe the first useful one won't be a single giant quantum computer...
COMPAMED has become the leading international marketplace for suppliers of medical manufacturing. The trade fair, which takes place every November and is co-located to MEDICA in Dusseldorf, has been steadily growing over the past years and shows that medical technology remains a rapidly growing market.
In 2016, the joint pavilion by the IVAM Microtechnology Network, the Product Market “High-tech for Medical Devices”, will be located in Hall 8a again and will...
14.10.2016 | Event News
14.10.2016 | Event News
12.10.2016 | Event News
24.10.2016 | Earth Sciences
24.10.2016 | Life Sciences
24.10.2016 | Physics and Astronomy