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 Subcutaneous Administration of Multispecific Antibody Makes Tumor Treatment Faster & More Tolerable
01.07.2015 | Helmholtz Zentrum München - Deutsches Forschungszentrum für Gesundheit und Umwelt

nachricht Why human egg cells don't age well
01.07.2015 | RIKEN

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Viaducts with wind turbines, the new renewable energy source

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...

Im Focus: X-rays and electrons join forces to map catalytic reactions in real-time

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...

Im Focus: Iron: A biological element?

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...

Im Focus: Thousands of Droplets for Diagnostics

Researchers develop new method enabling DNA molecules to be counted in just 30 minutes

A team of scientists including PhD student Friedrich Schuler from the Laboratory of MEMS Applications at the Department of Microsystems Engineering (IMTEK) of...

Im Focus: Bionic eye clinical trial results show long-term safety, efficacy vision-restoring implant

Patients using Argus II experienced significant improvement in visual function and quality of life

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...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

World Conference on Regenerative Medicine in Leipzig: Last chance to submit abstracts until 2 July

25.06.2015 | Event News

World Conference on Regenerative Medicine: Abstract Submission has been extended to 24 June

16.06.2015 | Event News

MUSE hosting Europe’s largest science communication conference

11.06.2015 | Event News

 
Latest News

Siemens acquires leading UK enforcement provider Zenco Systems

02.07.2015 | Press release

Viaducts with wind turbines, the new renewable energy source

02.07.2015 | Power and Electrical Engineering

NASA sees heavy rain in Tropical Cyclone Chan-Hom

02.07.2015 | Earth Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>