Featured Research

from universities, journals, and other organizations

Mechanism promoting multiple DNA mutations described by scientists

Date:
July 30, 2014
Source:
University of Iowa
Summary:
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 finding that cancer development often involves multiple mutations arising in clusters and in regions where chromosomal rearrangement takes place may one day lead to 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.

Related Articles


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.


Story Source:

The above story is based on materials provided by University of Iowa. Note: Materials may be edited for content and length.


Journal Reference:

  1. CynthiaJ. Sakofsky, StevenA. Roberts, Ewa Malc, PiotrA. Mieczkowski, MichaelA. Resnick, DmitryA. Gordenin, Anna Malkova. Break-Induced Replication Is a Source of Mutation Clusters Underlying Kataegis. Cell Reports, 2014; 7 (5): 1640 DOI: 10.1016/j.celrep.2014.04.053

Cite This Page:

University of Iowa. "Mechanism promoting multiple DNA mutations described by scientists." ScienceDaily. ScienceDaily, 30 July 2014. <www.sciencedaily.com/releases/2014/07/140730173130.htm>.
University of Iowa. (2014, July 30). Mechanism promoting multiple DNA mutations described by scientists. ScienceDaily. Retrieved October 24, 2014 from www.sciencedaily.com/releases/2014/07/140730173130.htm
University of Iowa. "Mechanism promoting multiple DNA mutations described by scientists." ScienceDaily. www.sciencedaily.com/releases/2014/07/140730173130.htm (accessed October 24, 2014).

Share This



More Health & Medicine News

Friday, October 24, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

IKEA Desk Converts From Standing to Sitting With One Button

IKEA Desk Converts From Standing to Sitting With One Button

Buzz60 (Oct. 24, 2014) IKEA is out with a new convertible desk that can convert from a sitting desk to a standing one with just the push of a button. Jen Markham explains. Video provided by Buzz60
Powered by NewsLook.com
Ebola Protective Suits Being Made in China

Ebola Protective Suits Being Made in China

AFP (Oct. 24, 2014) A factory in China is busy making Ebola protective suits for healthcare workers and others fighting the spread of the virus. Duration: 00:38 Video provided by AFP
Powered by NewsLook.com
WHO: Millions of Ebola Vaccine Doses by 2015

WHO: Millions of Ebola Vaccine Doses by 2015

AP (Oct. 24, 2014) The World Health Organization said on Friday that millions of doses of two experimental Ebola vaccines could be ready for use in 2015 and five more experimental vaccines would start being tested in March. (Oct. 24) Video provided by AP
Powered by NewsLook.com
Doctor in NYC Quarantined With Ebola

Doctor in NYC Quarantined With Ebola

AP (Oct. 24, 2014) An emergency room doctor who recently returned to the city after treating Ebola patients in West Africa has tested positive for the virus. He's quarantined in a hospital. (Oct. 24) Video provided by AP
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:

Breaking News:

Strange & Offbeat Stories


Health & Medicine

Mind & Brain

Living & Well

In Other News

... from NewsDaily.com

Science News

Health News

Environment News

Technology News



Save/Print:
Share:

Free Subscriptions


Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

Get Social & Mobile


Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

Have Feedback?


Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
Mobile: iPhone Android Web
Follow: Facebook Twitter Google+
Subscribe: RSS Feeds Email Newsletters
Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins