Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

How cells handle broken chromosomes

13.02.2009
Scientists from the Max Planck Institute of Biochemistry discovered a novel cellular response towards persistent DNA damage: After being recognized and initially processed by the cellular machinery, the broken chromosome is extensively scanned for homology and the break itself is later tethered to the nuclear envelope.

Thus the researchers uncovered a surprising feature of how DNA strand breaks can be handled. Their unexpected findings have important implications for the understanding of DNA repair mechanisms. (Molecular Cell 33, February 13th, 2009)

The central molecule for life is DNA, which constitutes the genetic blueprint of our organism. However, this precious molecule is constantly threatened by miscellaneous damage sources. DNA damage is a cause of cancer development, degenerative diseases and aging. The most dangerous and lethal type of DNA-damage is the DNA double strand break (DSB). A single DSB is enough to kill a cell or cause chromosomal aberrations leading to cancer.

Therefore, cells have evolved elaborate DNA repair systems that are fundamental for human health. DSBs can be repaired by error-prone non-homologous end joining, a pathway in which the DSB ends are simply fused together again. The alternative repair pathway, called homologous recombination, is mostly error-free and needs homologous DNA sequences to guide repair. A vast amount of research, by many scientists around the world, has provided us with a detailed picture of how the DNA damage is recognized and finally repaired. However, so far little was known, how homologous sequences are found and how cells react when DNA breaks persist.

Now, scientists around Stefan Jentsch, head of the Department of Molecular Cell Biology, were able to shed light on these questions, as they report in the upcoming issue of Molecular Cell.

The scientists modified a yeast strain in which a DSB can be induced and followed over time. Moreover, they managed to label the DNA-break for microscopic studies. Using high-resolution digital imaging, they observed after a few hours a directed movement of the break to the nuclear envelope. Jentsch and colleagues speculate that this tethering to the nuclear envelope could be a safety measure of cells to prevent erroneous and unwanted recombination events, which can have catastrophic consequences like cancer development or cell death.

Marian Kalocsay and Natalie Hiller, who conducted the study as part of their PhD-thesis research, then set out to unravel the molecular details of how a persistent DSB is recognized, processed and - at last - relocated to the nuclear envelope.

Using a high resolution method - the so called chip-on-chip technique - which allowed to investigate repair factor recruitment to DNA in unprecedented details, the researchers made a surprising observation: In an apparent attempt to find homology and repair the DSB, a protein called Rad51 (or "recombinase") begins within one hour to accumulate and to spread bi-directionally from the break, covering after a short time the entire chromosome - a much larger area than supposed before. "Intriguingly, Rad51 spreading only occurs on the chromosome where the break resides and does not "jump" to other chromosomes", says Kalocsay. As to the researchers knowledge, this is the first in vivo description of ongoing chromosome-wide homology search, which is the most mysterious event in DSB repair. Therefore, this finding has important implications for the understanding of DNA repair by homologous recombination.

Furthermore, Kalocsay and Hiller identified a novel important player in the DNA-damage response that is essential for Rad51 activation as well as for the relocation of DSBs to the nuclear envelope: the histone variant H2A.Z. In early stages of DNA repair it is incorporated into DNA near the DSBs and is essential there for the initiation of the following repair mechanisms. Later on, the attachment of the small modifying protein SUMO to H2A.Z plays an important role in the tethering of the break to the nuclear envelope. "Moreover, cells lacking H2A.Z are severely sensitive to DSBs, thus revealing H2A.Z as an important and novel factor in DSB-repair", explains Hiller.

Original Publication:
Marian Kalocsay*, Natalie Jasmin Hiller* and Stefan Jentsch: "Chromosome-Wide Rad51 Spreading and SUMO-H2A.Z-Dependent Chromosome Fixation in Response to a Persistent DNA Double-Strand Break"
Molecular Cell 33, 335-343, February 13, 2009 (doi:10.1016/j.molcel.2009.01.016).

*these authors contributed equally to the work

Eva-Maria Diehl
Public Relations
Max Planck Institute of Biochemistry
Am Klopferspitz 18
82152 Martinsried
phone: 089 - 8578 2824
email: diehl@biochem.mpg.de

Eva-Maria Diehl | Max-Planck-Institut
Further information:
http://www.biochem.mpg.de/jentsch
http://www.biochem.mpg.de

More articles from Life Sciences:

nachricht Megakaryocytes act as „bouncers“ restraining cell migration in the bone marrow
16.07.2019 | Rudolf-Virchow-Zentrum für Experimentelle Biomedizin der Universität Würzburg

nachricht A human liver cell atlas
15.07.2019 | Max Planck Institute of Immunobiology and Epigenetics

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Megakaryocytes act as „bouncers“ restraining cell migration in the bone marrow

Scientists at the University Würzburg and University Hospital of Würzburg found that megakaryocytes act as “bouncers” and thus modulate bone marrow niche properties and cell migration dynamics. The study was published in July in the Journal “Haematologica”.

Hematopoiesis is the process of forming blood cells, which occurs predominantly in the bone marrow. The bone marrow produces all types of blood cells: red...

Im Focus: Artificial neural network resolves puzzles from condensed matter physics: Which is the perfect quantum theory?

For some phenomena in quantum many-body physics several competing theories exist. But which of them describes a quantum phenomenon best? A team of researchers from the Technical University of Munich (TUM) and Harvard University in the United States has now successfully deployed artificial neural networks for image analysis of quantum systems.

Is that a dog or a cat? Such a classification is a prime example of machine learning: artificial neural networks can be trained to analyze images by looking...

Im Focus: Extremely hard yet metallically conductive: Bayreuth researchers develop novel material with high-tech prospects

An international research group led by scientists from the University of Bayreuth has produced a previously unknown material: Rhenium nitride pernitride. Thanks to combining properties that were previously considered incompatible, it looks set to become highly attractive for technological applications. Indeed, it is a super-hard metallic conductor that can withstand extremely high pressures like a diamond. A process now developed in Bayreuth opens up the possibility of producing rhenium nitride pernitride and other technologically interesting materials in sufficiently large quantity for their properties characterisation. The new findings are presented in "Nature Communications".

The possibility of finding a compound that was metallically conductive, super-hard, and ultra-incompressible was long considered unlikely in science. It was...

Im Focus: Modelling leads to the optimum size for platinum fuel cell catalysts: Activity of fuel cell catalysts doubled

An interdisciplinary research team at the Technical University of Munich (TUM) has built platinum nanoparticles for catalysis in fuel cells: The new size-optimized catalysts are twice as good as the best process commercially available today.

Fuel cells may well replace batteries as the power source for electric cars. They consume hydrogen, a gas which could be produced for example using surplus...

Im Focus: The secret of mushroom colors

Mushrooms: Darker fruiting bodies in cold climates

The fly agaric with its red hat is perhaps the most evocative of the diverse and variously colored mushroom species. Hitherto, the purpose of these colors was...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

2nd International Conference on UV LED Technologies & Applications – ICULTA 2020 | Call for Abstracts

24.06.2019 | Event News

SEMANTiCS 2019 brings together industry leaders and data scientists in Karlsruhe

29.04.2019 | Event News

Revered mathematicians and computer scientists converge with 200 young researchers in Heidelberg!

17.04.2019 | Event News

 
Latest News

Flying Laptop satellite mission extended by two years - Successfully in orbit since July 14, 2017

16.07.2019 | Physics and Astronomy

New safer, inexpensive way to propel small satellites

16.07.2019 | Power and Electrical Engineering

UCI electrical engineering team develops 'beyond 5G' wireless transceiver

16.07.2019 | Information Technology

VideoLinks
Science & Research
Overview of more VideoLinks >>>