Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Cell survival depends on chromosome integrity

10.07.2006
As part of a large National Institutes of Health-funded Technology Centers for Networks and Pathways project, Johns Hopkins researchers have discovered protein machinery important for cells to keep chromosomes intact. Without such proteins, their experiments show that yeast cells experience broken chromosomes and DNA damage that in human cells are well known to lead to cancer.

"Maintaining genome integrity is crucial for cell survival," says Jef Boeke, Ph.D., Sc.D., the report's senior author, a professor of molecular biology and genetics and co-director of the High Throughput Biology Center of the Institute for Basic Biomedical Sciences at Hopkins. The report will appear online July 6 in Current Biology.

Boeke and colleagues show that removing from yeast cells two proteins called sirtuins -- Hst3p and Hst4p -- causes cells to become hypersensitive to chemical agents and temperature and to spontaneously break and/or lose chromosomes. In humans, the loss or breakage of chromosomes can cause cells to lose control of when and if they are supposed to divide, becoming cancerous.

Nearly every human cell contains about six feet of DNA packaged into chromosomes. Chromosomes consist of DNA wrapped around a scaffold-like structure made of proteins called histones. Each time a cell divides into two, all of this DNA must be copied exactly and repackaged properly with histones to form chromosomes in the new cell.

During the copying process, new chromosomes often have breaks in them that need to be sealed before the chromosome is considered "finished" and the cell is ready to divide into two. All cells have damage control mechanisms that can sense nicks and breaks in chromosomes -- DNA damage -- and repair them.

"We think acetylation somehow marks the newly copied DNA so the cell knows to repair the breaks," says Boeke. "Once the breaks are repaired, the acetyl groups no longer are needed and are removed in normal cells."

Sirtuins Hst3p and Hst4p are proteins required to remove these specific chemical "decorations" -- called acetyl groups -- from specific sites on histones. The acetyl groups are added to lysine-56, an amino acid in the histone protein chain. Chromosomes in yeast cells missing Hst3p and Hst4p become hyperacetylated on lysine-56 -- it appears that every lysine-56 in every histone has attached an acetyl group.

"This is the first time we've ever seen such a huge effect," says Boeke. "The chromosomes just light up with acetyl groups -- they're just saturated" when cells are missing these sirtuins.

Earlier work showed that yeast cells initially need the lysine-56 decorations to repair breaks or other damage to DNA that occur when the DNA is copied, an essential process that also has the potential to seriously damage DNA. This new work shows that it is even more critical for yeast cells to remove these decorations once repair has been completed. Thus, there is an endless cycle of putting the acetyl groups on whenever there is damage or the danger thereof and taking them off again. Failure to take off the "decorations" leads to loss of entire chromosomes and other problems with the DNA.

Thus, yeast cells need to carefully coordinate acetylation and deacetylation of lysine-56.

The team concludes that by putting an acetyl group on lysine-56, the cell is signaling that its DNA is newly made and as a result possibly contains dangerous breaks. Acetylation on lysine-56 may be a universal mechanism for cells to mark damaged DNA. DNA damage can be caused by exposure to chemical mutagens, chemotherapy or even sunlight.

"There are a million mutagens in our environment," says Boeke. Once cells repair the DNA damage, it is important to shut off repair machinery and return to normal state. The cells require proteins like the sirtuins Hst3p and Hst4p to act as guideposts to help identify dangerous DNA lesions. If the DNA repair machinery does not fix these lesions to maintain chromosome integrity, the cell would lose control of growth or death.

Moving forward, the team hopes to further understand what controls these sirtuins to remove acetyl groups and how hyperacetylation can lead to such dramatic loss of chromosome integrity.

Audrey Huang | EurekAlert!
Further information:
http://www.jhmi.edu

More articles from Life Sciences:

nachricht More genes are active in high-performance maize
19.01.2018 | Rheinische Friedrich-Wilhelms-Universität Bonn

nachricht How plants see light
19.01.2018 | Albert-Ludwigs-Universität Freiburg im Breisgau

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Artificial agent designs quantum experiments

On the way to an intelligent laboratory, physicists from Innsbruck and Vienna present an artificial agent that autonomously designs quantum experiments. In initial experiments, the system has independently (re)discovered experimental techniques that are nowadays standard in modern quantum optical laboratories. This shows how machines could play a more creative role in research in the future.

We carry smartphones in our pockets, the streets are dotted with semi-autonomous cars, but in the research laboratory experiments are still being designed by...

Im Focus: Scientists decipher key principle behind reaction of metalloenzymes

So-called pre-distorted states accelerate photochemical reactions too

What enables electrons to be transferred swiftly, for example during photosynthesis? An interdisciplinary team of researchers has worked out the details of how...

Im Focus: The first precise measurement of a single molecule's effective charge

For the first time, scientists have precisely measured the effective electrical charge of a single molecule in solution. This fundamental insight of an SNSF Professor could also pave the way for future medical diagnostics.

Electrical charge is one of the key properties that allows molecules to interact. Life itself depends on this phenomenon: many biological processes involve...

Im Focus: Paradigm shift in Paris: Encouraging an holistic view of laser machining

At the JEC World Composite Show in Paris in March 2018, the Fraunhofer Institute for Laser Technology ILT will be focusing on the latest trends and innovations in laser machining of composites. Among other things, researchers at the booth shared with the Aachen Center for Integrative Lightweight Production (AZL) will demonstrate how lasers can be used for joining, structuring, cutting and drilling composite materials.

No other industry has attracted as much public attention to composite materials as the automotive industry, which along with the aerospace industry is a driver...

Im Focus: Room-temperature multiferroic thin films and their properties

Scientists at Tokyo Institute of Technology (Tokyo Tech) and Tohoku University have developed high-quality GFO epitaxial films and systematically investigated their ferroelectric and ferromagnetic properties. They also demonstrated the room-temperature magnetocapacitance effects of these GFO thin films.

Multiferroic materials show magnetically driven ferroelectricity. They are attracting increasing attention because of their fascinating properties such as...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

10th International Symposium: “Advanced Battery Power – Kraftwerk Batterie” Münster, 10-11 April 2018

08.01.2018 | Event News

See, understand and experience the work of the future

11.12.2017 | Event News

Innovative strategies to tackle parasitic worms

08.12.2017 | Event News

 
Latest News

Let the good tubes roll

19.01.2018 | Materials Sciences

How cancer metastasis happens: Researchers reveal a key mechanism

19.01.2018 | Health and Medicine

Meteoritic stardust unlocks timing of supernova dust formation

19.01.2018 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>