Featured Research

from universities, journals, and other organizations

Gene network illuminates stress, mutation and adaptation responses

Date:
December 6, 2012
Source:
Baylor College of Medicine
Summary:
Scientists have studied the puzzling response of bacteria to stress and the mutations that result. Now they can put together the pieces of that puzzle, describing most of the members of an elaborate gene network that functions in causing mutations during repair of double-stranded breaks in the DNA of stressed cells.

Simplified illustration of DNA. For much of her professional life, Dr. Susan Rosenberg has studied the puzzling response of bacteria to stress and the mutations that result. Now, she puts together the pieces of that puzzle, describing most of the members of an elaborate gene network that functions in causing mutations during repair of double-stranded breaks in the DNA of stressed cells.
Credit: Rodolfo Clix / Fotolia

For much of her professional life, Dr. Susan Rosenberg has studied the puzzling response of bacteria to stress and the mutations that result. In the current issue of the journal Science, she puts together the pieces of that puzzle, describing most of the members of an elaborate gene network that functions in causing mutations during repair of double-stranded breaks in the DNA of stressed cells.

Related Articles


"We now know the 93 genes more than half of which are funneling into three nodes that go down the mutagenesis pathway," said Rosenberg, professor of molecular and human genetics at Baylor College of Medicine and 2009 winner of the National Institutes of Health Director's Pioneer Award.

Groundbreaking work

Rosenberg's groundbreaking work has shown that the rate of mutation can be increased in response to stress such as starvation or environmental challenges such as antibiotics. This changes old ideas about constant and gradual accumulation of mutations over time. Some mutations are detrimental; others can promote survival. In this work, she and her colleagues sought to define the cellular pathways that result in this stress response.

"We screened for every gene in Escherichia coli that is needed to make this happen," said Rosenberg. E. coli is a "model" organism often used in the laboratory to study cells, because its DNA and other components work similarly to those in humans.

They have found that the mutagenic part of the process is not required to repair the broken DNA strands. When they "knock out" or remove the special "error-prone" DNA copying enzyme or polymerase, "the DNA is repaired beautifully and there are no mutations." So, cells do not make mutations because they have to, to repair DNA. Rather, this mechanism appears to regulate production of mutations, making more during stress, when cells are poorly adapted to their environments, and most likely to benefit from mutations.

Painstaking process

"Fewer than 16 proteins that are needed to accomplish stress-inducible mutagenesis were known previously. This is about the number known for any molecular mechanism of DNA biology," said Rosenberg. "Our screen sought the whole list of all proteins the cell uses to make it happen."

The painstaking process, begun by then postdoctoral fellow Dr. Mary-Jane Lombardo, now of Seres Health, Inc., in Cambridge, Mass., was completed by Dr. Amar Al Mamun, an assistant professor in Rosenberg's laboratory at BCM.

Large fractions of the network work "upstream" of the activation of the stress response, showing that these proteins apparently "sense" the stress. In delineating how the network functions, Rosenberg and her colleagues identified specific pathways through which the proteins sense the environment and connected them to the molecular mechanism that promotes the mutations.

Key factors revealed

The findings reveal key factors about the cells, such as that stress-response regulators act as key network hubs, she said. Most of the proteins in the network deal with whether or not the cells feel stress, said Rosenberg.

"The cell devotes a large number of proteins to controlling the process that generates diversity," she said. "And most of them are sensing the environment and coupling mutagenesis to stress."

They have determined the function of about half the network and are working on the rest.

"It's a resounding confirmation of the regulation of mutagenesis by stress responses, which causes mutations specifically when cells are maladapted to their environment when mutations might allow the cell to adapt," said Rosenberg.

Protein networks

It is also a demonstration that one can hope to detangle large protein networks into specific biological functions. Large protein networks are being discovered in many areas of biology, but what roles the proteins play in particular biological processes is often difficult to determine. Rosenberg's study shows that by working backwards from a defined molecular mechanism, they could assign roles to more than half the network proteins. Rosenberg thinks this strategy will be useful for many other protein networks.

Funding for this work came from grants from the National Institutes of Health and National Science Foundation.


Story Source:

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


Journal Reference:

  1. Abu Amar M. Al Mamun, Mary-Jane Lombardo, Chandan Shee, Andreas M. Lisewski, Caleb Gonzalez, Dongxu Lin, Ralf B. Nehring, Claude Saint-Ruf, Janet L. Gibson, Ryan L. Frisch, Olivier Lichtarge, P. J. Hastings, Susan M. Rosenberg. Identity and Function of a Large Gene Network Underlying Mutagenic Repair of DNA Breaks. Science, 7 December 2012: Vol. 338 no. 6112 pp. 1344-1348 DOI: 10.1126/science.1226683

Cite This Page:

Baylor College of Medicine. "Gene network illuminates stress, mutation and adaptation responses." ScienceDaily. ScienceDaily, 6 December 2012. <www.sciencedaily.com/releases/2012/12/121206142014.htm>.
Baylor College of Medicine. (2012, December 6). Gene network illuminates stress, mutation and adaptation responses. ScienceDaily. Retrieved October 31, 2014 from www.sciencedaily.com/releases/2012/12/121206142014.htm
Baylor College of Medicine. "Gene network illuminates stress, mutation and adaptation responses." ScienceDaily. www.sciencedaily.com/releases/2012/12/121206142014.htm (accessed October 31, 2014).

Share This



More Plants & Animals News

Friday, October 31, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

How A Chorus Led Scientists To A New Frog Species

How A Chorus Led Scientists To A New Frog Species

Newsy (Oct. 30, 2014) A frog noticed by a conservationist on New York's Staten Island has been confirmed as a new species after extensive study and genetic testing. Video provided by Newsy
Powered by NewsLook.com
Surfer Accidentally Stands on Shark, Gets Bitten

Surfer Accidentally Stands on Shark, Gets Bitten

AP (Oct. 30, 2014) A 20-year-old competition surfer said on Thursday he accidentally stepped on a shark's head before it bit him off the Australian east coast. (Oct. 30) Video provided by AP
Powered by NewsLook.com
Ebola Inflicts Heavy Toll on Guinean Potato Trade

Ebola Inflicts Heavy Toll on Guinean Potato Trade

AFP (Oct. 30, 2014) The Ebola epidemic has seen Senegal and Guinea Bissau close its borders with Guinea and the economic consequences have started to be felt, especially in Fouta Djallon, where the renowned potato industry has been hit hard. Duration: 02:01 Video provided by AFP
Powered by NewsLook.com
Genetically Altered Glowing Flower on Display in Tokyo

Genetically Altered Glowing Flower on Display in Tokyo

Reuters - Innovations Video Online (Oct. 30, 2014) Just in time for Halloween, a glowing flower goes on display in Tokyo. Instead of sorcery and magic, its creators used science to genetically modify the flower, adding a naturally fluorescent plankton protein to its genetic mix. Ben Gruber reports. Video provided by Reuters
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


Plants & Animals

Earth & Climate

Fossils & Ruins

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