Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

DNA repair teams' motto: 'To protect and serve'

20.11.2006
When you dial 911 you expect rescuers to pull up at your front door, unload and get busy--not park the truck down the street and eat donuts.

It's the same for a cell--just before it divides, it recruits protein complexes that repair breakage that may have occurred along the linear DNA chains making up your 46 chromosomes. Without repair, damage caused by smoking, chemical mutagens, or radiation might be passed on to the next generation.

However, in 2005, investigators at the Salk Institute for Biological Studies observed that before cell division some of these cellular paramedics inexplicably idle at undamaged chromosome ends, known as telomeres. Apparently the telomeres' disheveled appearance --resembling that of broken DNA strands--raises a red flag.

Now, in a study published in the Nov. 17 issue of Cell, that same team led by Jan Karlseder, Ph.D, Hearst Endowment Assistant Professor in the Molecular and Cell Biology Laboratory, reveals why those repair crews are parked at the ends of chromosomes and in doing so answer fundamental questions about how chromosomal stability is maintained.

... more about:
»Chromosome »DNA »Karlseder »Verdun »machinery »telomeres

After the 2005 study, says Karlseder, "We formed a hypothesis that after telomeres replicate they need to be detected by the internal DNA damage machinery--otherwise they cannot form a protective structure, or chromosomal cap."

And that's exactly what the new study shows. Examining activity of telomeric and DNA repair proteins in cultured human cells, the investigators found that right before cell division cellular repair proteins (including one actually called the 9-1-1 complex) are recruited to exposed DNA ends. But rather than fixing what resembles a break, the repair crew, which first arrived at the scene, calls in a second conglomeration of repair proteins. This one, called the homologous recombination (HR) machinery, creates the protective structure.

"The HR machinery fixes any break in the genome that occurs during replication of DNA," explains post-doctoral researcher Ramiro Verdun, Ph.D., lead author of the 2005 and the current study. However, at telomeres, just before they unload their cellular repair truck, HR crews apparently realize where they are--at the end and not the middle of the DNA strand-- and reconfigure. "At telomeres, they invade and then stop," says Verdun. "They adopt a different strategy."

That strategy is to tuck in the ragged chromosomal tips and form the cap, thereby hiding those tips from enzymes whose job it is to reattach errant DNA strands. "Again it was surprising," says Karlseder of the versatile HR team. "The cell is very clever. It takes advantage of a machinery that's already there and whose job it is to repair damage, but at telomeres this machinery fulfills a very special 'repair' function."

Be thankful your cells are so clever. Erroneous fusion of chromosome ends would be disastrous, leading to cell death or worse. "When DNA at telomeres is repaired chromosomes fuse together. If these cells then divide you could get chromosome breakage and genome instability, which leads to cancer," explains Karlseder.

In fact, the reason that telomeres, which are synthesized by an enzyme known as telomerase, exist is to assure that chromosome ends remain intact through a lifetime of cell divisions. When asked if there are cancers in which telomerase activity goes awry, Karlseder answers with no hesitation: "Almost all of them."

In fact, many proteins contained in DNA repair complexes are defective in cancer. "Proteins that play an important role in the model we propose are mutated in several diseases," says Verdun. "In cells with those mutations, the telomeres are not normal--they are fused, broken, shorter, or longer--but they are not normal."

For Verdun one goal of basic science is to understand how normal cells behave with the goal of fixing them if something goes wrong. "We are working on normal human cells--not cancer cells," he explains. "But we cannot understand how badly behaved cancer cells work if we don't know how a normal cell functions."

Gina Kirchweger | EurekAlert!
Further information:
http://www.salk.edu

Further reports about: Chromosome DNA Karlseder Verdun machinery telomeres

More articles from Life Sciences:

nachricht Topologische Quantenchemie
21.07.2017 | Max-Planck-Institut für Chemische Physik fester Stoffe

nachricht Topological Quantum Chemistry
21.07.2017 | Max-Planck-Institut für Chemische Physik fester Stoffe

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Manipulating Electron Spins Without Loss of Information

Physicists have developed a new technique that uses electrical voltages to control the electron spin on a chip. The newly-developed method provides protection from spin decay, meaning that the contained information can be maintained and transmitted over comparatively large distances, as has been demonstrated by a team from the University of Basel’s Department of Physics and the Swiss Nanoscience Institute. The results have been published in Physical Review X.

For several years, researchers have been trying to use the spin of an electron to store and transmit information. The spin of each electron is always coupled...

Im Focus: The proton precisely weighted

What is the mass of a proton? Scientists from Germany and Japan successfully did an important step towards the most exact knowledge of this fundamental constant. By means of precision measurements on a single proton, they could improve the precision by a factor of three and also correct the existing value.

To determine the mass of a single proton still more accurate – a group of physicists led by Klaus Blaum and Sven Sturm of the Max Planck Institute for Nuclear...

Im Focus: On the way to a biological alternative

A bacterial enzyme enables reactions that open up alternatives to key industrial chemical processes

The research team of Prof. Dr. Oliver Einsle at the University of Freiburg's Institute of Biochemistry has long been exploring the functioning of nitrogenase....

Im Focus: The 1 trillion tonne iceberg

Larsen C Ice Shelf rift finally breaks through

A one trillion tonne iceberg - one of the biggest ever recorded -- has calved away from the Larsen C Ice Shelf in Antarctica, after a rift in the ice,...

Im Focus: Laser-cooled ions contribute to better understanding of friction

Physics supports biology: Researchers from PTB have developed a model system to investigate friction phenomena with atomic precision

Friction: what you want from car brakes, otherwise rather a nuisance. In any case, it is useful to know as precisely as possible how friction phenomena arise –...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Closing the Sustainability Circle: Protection of Food with Biobased Materials

21.07.2017 | Event News

»We are bringing Additive Manufacturing to SMEs«

19.07.2017 | Event News

The technology with a feel for feelings

12.07.2017 | Event News

 
Latest News

NASA looks to solar eclipse to help understand Earth's energy system

21.07.2017 | Earth Sciences

Stanford researchers develop a new type of soft, growing robot

21.07.2017 | Power and Electrical Engineering

Vortex photons from electrons in circular motion

21.07.2017 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>