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.

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 22, 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 22, 2014).

Share This



More Health & Medicine News

Wednesday, October 22, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Orthodontist Mom Jennifer Salzer on the Best Time for Braces

Orthodontist Mom Jennifer Salzer on the Best Time for Braces

Working Mother (Oct. 22, 2014) Is your child ready? Video provided by Working Mother
Powered by NewsLook.com
U.S. Issues Ebola Travel Restrictions, Are Visa Bans Next?

U.S. Issues Ebola Travel Restrictions, Are Visa Bans Next?

Newsy (Oct. 22, 2014) Now that the U.S. is restricting travel from West Africa, some are dropping questions about a travel ban and instead asking about visa bans. Video provided by Newsy
Powered by NewsLook.com
US to Track Everyone Coming from Ebola Nations

US to Track Everyone Coming from Ebola Nations

AP (Oct. 22, 2014) Stepping up their vigilance against Ebola, federal authorities said Wednesday that everyone traveling into the US from Ebola-stricken nations will be monitored for symptoms for 21 days. (Oct. 22) Video provided by AP
Powered by NewsLook.com
Doctors Help Paralysed Man Walk Again, Patient in Disbelief

Doctors Help Paralysed Man Walk Again, Patient in Disbelief

AFP (Oct. 22, 2014) Polish doctors describe how they helped a paralysed man walk again, with the patient in disbelief at the return of sensation to his legs. Duration: 1:04 Video provided by AFP
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