Navigation Links
New insights into DNA repair process may spur better cancer therapies

DURHAM, N.C. By detailing a process required for repairing DNA breakage, scientists at the Duke Cancer Institute have gained a better understanding of how cells deal with the barrage of damage that can contribute to cancer and other diseases.

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."


Contact: Sarah Avery
Duke University Medical Center

Related biology news :

1. Erratic proteins: New insights into a transport mechanism
2. Eyewear Market 2014 Insights and System Refresher Report
3. Global analysis reveals new insights into the ribosome -- with important implications for disease
4. Potential diagnostic marker for zinc status offers insights into the effects of zinc deficiency
5. New insights into neuroblastoma tumor suppressor may provide clues for improved treatment
6. UCLA life scientists present new insights on climate change and species interactions
7. Insights into deadly coral bleaching could help preserve reefs
8. New insights into how genes turn on and off
9. New insights into the development of the heart
10. Peach genome offers insights into breeding strategies for biofuels crops
11. Novel insights into the evolution of protein networks
Post Your Comments:
(Date:11/9/2015)... Nov. 9, 2015  Synaptics Inc. (NASDAQ: SYNA ... announced broader entry into the automotive market with a ... the pace of consumer electronics human interface innovation. Synaptics, ... ideal for the automotive industry and will be implemented ... Europe , Japan , ...
(Date:10/29/2015)... 29, 2015  The J. Craig Venter Institute (JCVI) ... Synthesis and Biosecurity: Lessons Learned and Options for the ... and Human Services guidance for synthetic biology providers has ... --> --> Synthetic biology ... potential to pose unique biosecurity threats. It now is ...
(Date:10/29/2015)... NXTD ) ("NXT-ID" or ... the growing mobile commerce market and creator of ... leading marketplace to discover and buy innovative technology ... on StackSocial for this holiday season.   ... a biometric authentication company focused on the growing ...
Breaking Biology News(10 mins):
(Date:11/24/2015)... HemoShear Therapeutics, LLC, a privately held ... disorders, announced today the appointment of H. ... (BOD). Mr. Watkins is the former president and ... and also served as the chairman of the ... Chairman and CEO of HemoShear Therapeutics. "The combination ...
(Date:11/24/2015)... ... 2015 , ... Whitehouse Laboratories is pleased to announce that it has completed ... strictly dedicated to basic USP 61, USP 62 and USP 51 testing specific to ... chemistry and micro testing performed by one supplier. Management has formally announced ...
(Date:11/23/2015)... Ceres, Inc . (Nasdaq: CERE ), an agricultural ... year ended August 31, 2015 and provided an update ... --> During fiscal year 2015, Ceres refocused its ... better balance of yield, energy and nutrition. Among other ... crop input providers and made significant progress in advancing ...
(Date:11/23/2015)... , ... November 23, 2015 , ... Noblis, Inc., a ... former Director, Plans and Programs, National Geospatial Intelligence Agency (NGA), has joined the Noblis ... an incredibly distinguished career in the intelligence community and the private sector,” said ...
Breaking Biology Technology: