Featured Research

from universities, journals, and other organizations

Raising The Alarm When DNA Goes Bad: 'Rapid Response Team' Monitors And Quickly Responds To DNA Damage

Date:
August 22, 2009
Source:
European Molecular Biology Laboratory
Summary:
Scientists have known for a long time that when DNA is damaged, a key enzyme sets off a cellular "alarm bell" to alert the cell to start the repair process, but until recently little was known about how the cell detects and responds to this alarm. In a new study, researchers have identified a whole family of proteins capable of a direct response to the alarm signal.

Macrodomain-containing proteins rapidly respond to DNA damage: An ultraviolet laser is used to damage DNA within a human cell. This is a still image from a movie showing how a fluorescent version of a macrodomain-containing protein (labelled Af1521 here) rapidly accumulates at the site of DNA damage.
Credit: Image copyrighted EMBL

Our genome is constantly under attack from things like UV light and toxins, which can damage or even break DNA strands and ultimately lead to cancer and other diseases. Scientists have known for a long time that when DNA is damaged, a key enzyme sets off a cellular ‘alarm bell’ to alert the cell to start the repair process, but until recently little was known about how the cell detects and responds to this alarm.

In a study published in Nature Structural and Molecular Biology, researchers at the European Molecular Biology Laboratory (EMBL) in Heidelberg, Germany, have identified a whole family of proteins capable of a direct response to the alarm signal.

Our genome is a huge repository of information guiding the construction and function of all the cells in our bodies. Cells sustain many hits to their DNA every day, which can lead tomutations, so they maintain a fleet of DNA repair machinery that can be rapidly mobilised and sent to damaged sites in an emergency.

Because our DNA is so long and unwieldy, it needs to be packaged up with proteins and organised into a complex structure called chromatin. Scientists have known for 50 years that one component of chromatin, an enzyme known as PARP1, is activated by DNA damage and produces a molecular signal, called PAR, which raises the alarm at the site of the damage. In recent weeks, scientists have for the first time worked out how PAR is rapidly detected by the cell; in their Nature Structural and Molecular Biology paper, the group of Andreas Ladurner and their colleagues at EMBL have identified a whole family of proteins that respond to this signal by binding to it directly.

What these proteins share is a special region called a macrodomain. By using a laser to reproduce DNA damage in the lab, the scientists were able to follow fluorescently-labelled macrodomain proteins in cells and observed that they quickly move to the site of DNA damage. A high-resolution image, obtained by X-ray crystallography, shows how the macrodomain forms a ‘pocket’ fitting the PAR signal exactly.

Among the members of the family the researchers found a protein called histone macroH2A1.1. “This was very surprising. Histones play a major role in assembling chromatin and keeping it together, but they don’t usually have macrodomains,” says Ladurner. “The finding is particularly relevant, because it turns out that cancer cells don’t have macroH2A1.1. The fact that one member of the rapid response team that detects DNA damage is missing could contribute to the disease.”

Because macroH2A1.1 is embedded in chromatin, when it recognises PAR at DNA damage sites, it drags the complex but highly-organised tangle of chromatin with it. As a result, macroH2A1.1 condenses the chromatin environment around the damaged area.

The scientists are now trying to understand why this happens. One plausible explanation could be that by temporarily compacting the DNA, the broken ends of the DNA molecule are kept closer together. This should increase the chances of being able to repair it.

“With these findings we’ve opened up completely new perspectives to a fifty-year-old field of research,” says Ladurner. “We’re very excited of what lies ahead and hope that we’ll soon be much closer in understanding how PARP1 and macrodomains together maintain a healthy genome.”


Story Source:

The above story is based on materials provided by European Molecular Biology Laboratory. Note: Materials may be edited for content and length.


Cite This Page:

European Molecular Biology Laboratory. "Raising The Alarm When DNA Goes Bad: 'Rapid Response Team' Monitors And Quickly Responds To DNA Damage." ScienceDaily. ScienceDaily, 22 August 2009. <www.sciencedaily.com/releases/2009/08/090813170854.htm>.
European Molecular Biology Laboratory. (2009, August 22). Raising The Alarm When DNA Goes Bad: 'Rapid Response Team' Monitors And Quickly Responds To DNA Damage. ScienceDaily. Retrieved July 31, 2014 from www.sciencedaily.com/releases/2009/08/090813170854.htm
European Molecular Biology Laboratory. "Raising The Alarm When DNA Goes Bad: 'Rapid Response Team' Monitors And Quickly Responds To DNA Damage." ScienceDaily. www.sciencedaily.com/releases/2009/08/090813170854.htm (accessed July 31, 2014).

Share This




More Health & Medicine News

Thursday, July 31, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Health Insurers' Profits Slide

Health Insurers' Profits Slide

Reuters - Business Video Online (July 30, 2014) Obamacare-related costs were said to be behind the profit plunge at Wellpoint and Humana, but Wellpoint sees the new exchanges boosting its earnings for the full year. Fred Katayama reports. Video provided by Reuters
Powered by NewsLook.com
Peace Corps Pulls Workers From W. Africa Over Ebola Fears

Peace Corps Pulls Workers From W. Africa Over Ebola Fears

Newsy (July 30, 2014) The Peace Corps is one of several U.S.-based organizations to pull workers out of West Africa because of the Ebola outbreak. Video provided by Newsy
Powered by NewsLook.com
Weather Kills 2K A Year, But Storms Aren't The Main Offender

Weather Kills 2K A Year, But Storms Aren't The Main Offender

Newsy (July 30, 2014) Health officials say 2,000 deaths occur each year in the U.S. due to weather, but it's excessive heat and cold that claim the most lives. Video provided by Newsy
Powered by NewsLook.com
Concern Grows Over Worsening Ebola Crisis

Concern Grows Over Worsening Ebola Crisis

AFP (July 30, 2014) Pan-African airline ASKY has suspended all flights to and from the capitals of Liberia and Sierra Leone amid the worsening Ebola health crisis, which has so far caused 672 deaths in Guinea, Liberia and Sierra Leone. Duration: 00:43 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:
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