Featured Research

from universities, journals, and other organizations

New Step In DNA Damage Response In Neurons Discovered

Date:
January 21, 2009
Source:
Emory University
Summary:
Mutations in the ATM gene cause neurological problems combined with immune deficiency and radiation sensitivity in humans. ATM controls cells' response to DNA damage in several cell types. Cdk5, involved in several neurodegenerative diseases, is required to activate ATM.

Researchers have identified a biochemical switch required for nerve cells to respond to DNA damage.

The finding illuminates a connection between proteins involved in neurodegenerative disease and in cells' response to DNA damage.

Most children with the inherited disease ataxia telangiectasia are wheelchair-bound by age 10 because of neurological problems. Patients also have weakened immune systems and more frequent leukemias, and are more sensitive to radiation.

The underlying problem comes from mutations in the ATM (ataxia telangiectasia mutated) gene, which encodes an enzyme that controls cells' response to and repair of DNA damage.

ATM can be turned on experimentally by treating cells with chemicals that damage DNA. After other proteins in the cell detected broken DNA needing repair, scientists had thought that the ATM protein could activate itself directly. Emory researchers have shown that an additional step is necessary first.

"In neurons that are not dividing anymore, we now know that another regulator is involved: Cdk5," says Zixu Mao, MD, PhD, associate professor of pharmacology and neurology at Emory University School of Medicine.

Working with postdoctoral fellows Bo Tian, PhD and Qian Yang, PhD, Mao found that the Cdk5 protein must activate ATM before ATM can do its job in neurons.

The results support the idea that Cdk5 may be a potential drug target. Cdk5 contributes to normal brain development, and aberrant Cdk5 activity is known to be involved in the death of neurons in several neurodegenerative diseases, including Alzheimer's, Parkinson's and amyotrophic lateral sclerosis.

"Cdk5 has a complex character," Mao says. "It can be bad for neurons if its activity is either too high or too low."

Mao says he and his colleagues were intrigued by reports that in these diseases, neurons that had stopped dividing appear to restart that process, copying their DNA, before dying.

"That's what really kicked us into high gear," he says.

The same process, called "mitotic catastrophe," occurs when neurons suffer DNA damage. Inhibiting either Cdk5 or ATM can reduce the number of neurons that suffer mitotic catastrophe after DNA damage, the authors found.

The National Institutes of Health and the Woodruff Health Sciences Center Fund supported the research.


Story Source:

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


Journal Reference:

  1. Tian et al. Phosphorylation of ATM by Cdk5 mediates DNA damage signalling and regulates neuronal death. Nature Cell Biology, 2009; DOI: 10.1038/ncb1829

Cite This Page:

Emory University. "New Step In DNA Damage Response In Neurons Discovered." ScienceDaily. ScienceDaily, 21 January 2009. <www.sciencedaily.com/releases/2009/01/090118200642.htm>.
Emory University. (2009, January 21). New Step In DNA Damage Response In Neurons Discovered. ScienceDaily. Retrieved July 25, 2014 from www.sciencedaily.com/releases/2009/01/090118200642.htm
Emory University. "New Step In DNA Damage Response In Neurons Discovered." ScienceDaily. www.sciencedaily.com/releases/2009/01/090118200642.htm (accessed July 25, 2014).

Share This




More Health & Medicine News

Friday, July 25, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

New Painkiller Designed To Discourage Abuse: Will It Work?

New Painkiller Designed To Discourage Abuse: Will It Work?

Newsy (July 24, 2014) The FDA approved Targiniq ER on Wednesday, a painkiller designed to keep users from abusing it. Like any new medication, however, it has doubters. Video provided by Newsy
Powered by NewsLook.com
Doctor At Forefront Of Fighting Ebola Outbreak Gets Ebola

Doctor At Forefront Of Fighting Ebola Outbreak Gets Ebola

Newsy (July 24, 2014) Sheik Umar Khan has treated many of the people infected in the Ebola outbreak, and now he's become one of them. Video provided by Newsy
Powered by NewsLook.com
Condemned Man's US Execution Takes Nearly Two Hours

Condemned Man's US Execution Takes Nearly Two Hours

AFP (July 24, 2014) America's death penalty debate raged Thursday after it took nearly two hours for Arizona to execute a prisoner who lost a Supreme Court battle challenging the experimental lethal drug cocktail. Duration: 00:55 Video provided by AFP
Powered by NewsLook.com
Can Watching TV Make You Feel Like A Failure?

Can Watching TV Make You Feel Like A Failure?

Newsy (July 24, 2014) A study by German researchers claims watching TV while you're stressed out can make you feel guilty and like a failure. Video provided by Newsy
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:
from the past week

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