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Raising The Alarm When DNA Goes Bad: 'Rapid Response Team' Monitors And Quickly Responds To DNA Damage
ScienceDaily (Aug. 22, 2009) — 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.
See also:
Health & Medicine
* Genes
* Human Biology
* Forensics
Plants & Animals
* Biochemistry Research
* Biology
* Biotechnology
Reference
* Heat shock protein
* Tumor suppressor gene
* Antifreeze protein
* Vector (biology)
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.”
Adapted from materials provided by European Molecular Biology Laboratory.
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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)
Related Stories
DNA-damaged Cells Communicate With Neighbors To Let Them Know They're In Trouble (July 14, 2009) — When cells experiencing DNA damage fail to repair themselves, they send a signal to their neighbors letting them know they're in trouble. The discovery, which shows that a process dubbed the DDR (DNA ... > read more
Alarm Pheromone Causes Aphids To Sprout Wings (May 19, 2005) — When aphids are attacked by predators such as ladybird beetles, they release an alarm pheromone that has long been known to cause other aphids to walk around or drop from the plant. In a paper soon ... > read more
Refusal Of Suicide Order: Why Tumor Cells Become Resistant (June 24, 2008) — Cells with irreparable DNA damage normally induce programmed cell death, or apoptosis. However, this mechanism often fails in tumor cells so that transformed cells are able to multiply and spread ... > read more
New View Of DNA Repair: Enzyme Alerts Cell's Powerful Army To Repair DNA Damage (Sep. 9, 2007) — Each day cells detect and repair daily assaults to our DNA. Researchers have discovered that a well-known enzyme scans genes for damage and alerts the major cancer suppressor protein p53. The finding ... > read more
Skin Defects Set Off Alarm With Widespread And Potentially Harmful Effects (June 1, 2008) — When patches of red, flaky and itchy skin on newborn mice led rapidly to their deaths, researchers looked for the reason why. What they found was a molecular alarm system that serves as a sentinel to ... > read more
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Raising The Alarm When DNA Goes Bad: 'Rapid Response Team' Monitors And Quickly Responds To DNA Damage
ScienceDaily (Aug. 22, 2009) — 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.
See also:
Health & Medicine
* Genes
* Human Biology
* Forensics
Plants & Animals
* Biochemistry Research
* Biology
* Biotechnology
Reference
* Heat shock protein
* Tumor suppressor gene
* Antifreeze protein
* Vector (biology)
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.”
Adapted from materials provided by European Molecular Biology Laboratory.
Email or share this story:
| More
Need to cite this story in your essay, paper, or report? Use one of the following formats:
APA
MLA
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)
Related Stories
DNA-damaged Cells Communicate With Neighbors To Let Them Know They're In Trouble (July 14, 2009) — When cells experiencing DNA damage fail to repair themselves, they send a signal to their neighbors letting them know they're in trouble. The discovery, which shows that a process dubbed the DDR (DNA ... > read more
Alarm Pheromone Causes Aphids To Sprout Wings (May 19, 2005) — When aphids are attacked by predators such as ladybird beetles, they release an alarm pheromone that has long been known to cause other aphids to walk around or drop from the plant. In a paper soon ... > read more
Refusal Of Suicide Order: Why Tumor Cells Become Resistant (June 24, 2008) — Cells with irreparable DNA damage normally induce programmed cell death, or apoptosis. However, this mechanism often fails in tumor cells so that transformed cells are able to multiply and spread ... > read more
New View Of DNA Repair: Enzyme Alerts Cell's Powerful Army To Repair DNA Damage (Sep. 9, 2007) — Each day cells detect and repair daily assaults to our DNA. Researchers have discovered that a well-known enzyme scans genes for damage and alerts the major cancer suppressor protein p53. The finding ... > read more
Skin Defects Set Off Alarm With Widespread And Potentially Harmful Effects (June 1, 2008) — When patches of red, flaky and itchy skin on newborn mice led rapidly to their deaths, researchers looked for the reason why. What they found was a molecular alarm system that serves as a sentinel to ... > read more
Search ScienceDaily
Number of stories in archives: 44,032
Find with keyword(s):
Enter a keyword or phrase to search ScienceDaily's archives for related news topics,
the latest news stories, reference articles, science videos, images, and books.
Just In:
Lightning's Mirror Image ... Only Much Bigger
Using Light To Teach Magnets New Tricks
Research May Point To 'Off Switch' For Cancer
Microchip Does 1,000 Chemical Reactions At Once
Naming Evolution's Winners And Losers
Inner 'Fingerprint' For Personal Medical Care
Why Sleep? To Boost Efficiency, Minimize Risk
Ultrathin LEDs: New Class Of Displays
Science Video News
Baking Out DNA
Forensic scientists analyzing bones found in the Gobi desert discovered that the DNA within them could be surprisingly easily extracted. In an. ... > full story
* Researchers Apply DNA Biology to Vaccination Technique
* Civil Engineers Track Roaming Cell Phones to Monitor Traffic
* Scientists Show Blue Light Can Help Reset Sleep Cycle
* more science videos
Breaking News
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* S.Korea seeks 4-year prison term for stem cell fraud
* Encyclopedia of Life grows; clues on ageing, pests
* Satellites put into orbit for Japan and Australia
* Scientists make "sugar bug" drug for bowel disease
* Gene swap experiment makes altering bugs easier
* more science news
In Other News ...
* Facebook to boost staff by 50% in 2009: report
* Netanyahu sees talks with Palestinians in 2 months
* Justice Dept advises pursuing CIA abuses: report
* Suspect in U.S. model murder found dead in Canada
* Storm Bill loses steam in North Atlantic
* Fires near Athens recede after 3-day inferno
* Malaysian state to cane woman after Ramadan
* U.S. presses sanctions to end N.Korea atomic plans
* more top news
Copyright Reuters 2008. See Restrictions.
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