Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Biologists describe mechanism promoting multiple DNA mutations

31.07.2014

Research could lead to development of new cancer therapies

DNA mutations—long known to fuel cancer as well as evolutionary changes in a living organism—had been thought to be rare events that occur randomly throughout the genome.

However, recent studies have shown that cancer development frequently involves the formation of multiple mutations that arise simultaneously and in close proximity to each other. These groups of clustered mutations are frequently found in regions where chromosomal rearrangements take place.

The discovery, published in the journal Cell Reports, may one day lead to new cancer therapies, according to a University of Iowa biologist and her colleagues, and a group of researchers from the National Institute of Environmental Health Sciences led by Senior Associate Scientist Dmitry Gordenin.

The formation of clustered mutations may result from the process of DNA repair.

Anna Malkova, associate professor of biology in the UI College of Liberal Arts and Sciences, notes that the DNA repair pathway, known as break-induced replication (BIR), can promote clusters of DNA mutations.

“Previously, we have shown that double-strand DNA breaks, which can result from oxidation, ionizing radiation and replication errors, can be repaired by BIR,” says Malkova.

“During BIR, one broken DNA end is paired with an identical DNA sequence on another chromosome and initiates an unusual type of replication, which proceeds as a migrating bubble and is associated with the accumulation of large amounts of single-strand DNA,” she says.

In the Cell Reports study, researchers subjected yeast cells undergoing BIR to alkylating (cancer cell-killing agents) damage. “We found that the single-stranded DNA regions that accumulate during BIR are susceptible to damage that leads to the formation of mutation clusters,” explains Cynthia Sakofsky, postdoctoral fellow at the UI and one of two co-first authors on the paper. “These clusters are similar to those found in human cancer,” she says.

Importantly, say the researchers, the paper provides a mechanism to potentially explain how genetic changes form in human cancers. Thus, it will be critical for future research to determine whether BIR can form clustered mutations that lead to cancer in humans. If this turns out to be true, it may lead to the discovery of new targets for developing therapies against human cancers.

In addition to Malkova, Gordenin and Sakofsky, co-authors of the paper are: Steven A. Roberts, co-first author, and Michael A. Resnick, both of the National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina; and Ewa Malc and Piotr A. Mieczkowski, both of the Department of Genetics, Lineberger Comprehensive Cancer Center and Carolina Center for Genome Sciences, University of North Carolina, Chapel Hill, North Carolina.

The paper, titled “Break-Induced Replication Is a Source of Mutation Clusters Underlying Kataegis,” was published in the May 29 issue of Cell Reports.

The research was funded by NIH grants R01GM084242 (to A.M.) and 5R01GM052319-17 (to P.A.M.) and by the Intramural Research Program of the NIH, National Institute of Environmental Health Sciences (project ES065073, to M.A.R). S.A.R. was supported by NIH Pathway to Independence Award K99ES022633-01.

Contacts

Anna Malkova, Department of Biology, 319-384-1285
Gary Galluzzo, Strategic Communications, 319-384-0009

Gary Galluzzo | Eurek Alert!
Further information:
http://now.uiowa.edu/2014/07/biologists-describe-mechanism-promoting-multiple-dna-mutations

Further reports about: Cell DNA Environmental clusters damage mechanism mutations repair replication

More articles from Life Sciences:

nachricht An evolutionary heads-up – The brain size advantage
22.05.2015 | Veterinärmedizinische Universität Wien

nachricht Endocrine disrupting chemicals in baby teethers
21.05.2015 | Goethe-Universität Frankfurt am Main

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Basel Physicists Develop Efficient Method of Signal Transmission from Nanocomponents

Physicists have developed an innovative method that could enable the efficient use of nanocomponents in electronic circuits. To achieve this, they have developed a layout in which a nanocomponent is connected to two electrical conductors, which uncouple the electrical signal in a highly efficient manner. The scientists at the Department of Physics and the Swiss Nanoscience Institute at the University of Basel have published their results in the scientific journal “Nature Communications” together with their colleagues from ETH Zurich.

Electronic components are becoming smaller and smaller. Components measuring just a few nanometers – the size of around ten atoms – are already being produced...

Im Focus: IoT-based Advanced Automobile Parking Navigation System

Development and implementation of an advanced automobile parking navigation platform for parking services

To fulfill the requirements of the industry, PolyU researchers developed the Advanced Automobile Parking Navigation Platform, which includes smart devices,...

Im Focus: First electrical car ferry in the world in operation in Norway now

  • Siemens delivers electric propulsion system and charging stations with lithium-ion batteries charged from hydro power
  • Ferry only uses 150 kilowatt hours (kWh) per route and reduces cost of fuel by 60 percent
  • Milestone on the road to operating emission-free ferries

The world's first electrical car and passenger ferry powered by batteries has entered service in Norway. The ferry only uses 150 kWh per route, which...

Im Focus: Into the ice – RV Polarstern opens the arctic season by setting course for Spitsbergen

On Tuesday, 19 May 2015 the research icebreaker Polarstern will leave its home port in Bremerhaven, setting a course for the Arctic. Led by Dr Ilka Peeken from the Alfred Wegener Institute, Helmholtz Centre for Polar and Marine Research (AWI) a team of 53 researchers from 11 countries will investigate the effects of climate change in the Arctic, from the surface ice floes down to the seafloor.

RV Polarstern will enter the sea-ice zone north of Spitsbergen. Covering two shallow regions on their way to deeper waters, the scientists on board will focus...

Im Focus: Gel filled with nanosponges cleans up MRSA infections

Nanoengineers at the University of California, San Diego developed a gel filled with toxin-absorbing nanosponges that could lead to an effective treatment for skin and wound infections caused by MRSA (methicillin-resistant Staphylococcus aureus), an antibiotic-resistant bacteria. This "nanosponge-hydrogel" minimized the growth of skin lesions on mice infected with MRSA - without the use of antibiotics. The researchers recently published their findings online in Advanced Materials.

To make the nanosponge-hydrogel, the team mixed nanosponges, which are nanoparticles that absorb dangerous toxins produced by MRSA, E. coli and other...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

International symposium: trends in spatial analysis and modelling for a more sustainable land use

20.05.2015 | Event News

15th conference of the International Association of Colloid and Interface Scientists

18.05.2015 | Event News

EHFG 2015: Securing health in Europe. Balancing priorities, sharing responsibilities

12.05.2015 | Event News

 
Latest News

Mesoporous Particles for the Development of Drug Delivery System Safe to Human Bodies

22.05.2015 | Materials Sciences

Computing at the Speed of Light

22.05.2015 | Information Technology

Development of Gold Nanoparticles That Control Osteogenic Differentiation of Stem Cells

22.05.2015 | Materials Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>