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 In focus: Peptides, the “little brothers and sisters” of proteins
12.11.2018 | Technische Universität Berlin

nachricht How to produce fluorescent nanoparticles for medical applications in a nuclear reactor
09.11.2018 | Institute of Organic Chemistry and Biochemistry of the Czech Academy of Sciences (IOCB Prague)

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: A Leap Into Quantum Technology

Faster and secure data communication: This is the goal of a new joint project involving physicists from the University of Würzburg. The German Federal Ministry of Education and Research funds the project with 14.8 million euro.

In our digital world data security and secure communication are becoming more and more important. Quantum communication is a promising approach to achieve...

Im Focus: Research icebreaker Polarstern begins the Antarctic season

What does it look like below the ice shelf of the calved massive iceberg A68?

On Saturday, 10 November 2018, the research icebreaker Polarstern will leave its homeport of Bremerhaven, bound for Cape Town, South Africa.

Im Focus: Penn engineers develop ultrathin, ultralight 'nanocardboard'

When choosing materials to make something, trade-offs need to be made between a host of properties, such as thickness, stiffness and weight. Depending on the application in question, finding just the right balance is the difference between success and failure

Now, a team of Penn Engineers has demonstrated a new material they call "nanocardboard," an ultrathin equivalent of corrugated paper cardboard. A square...

Im Focus: Coping with errors in the quantum age

Physicists at ETH Zurich demonstrate how errors that occur during the manipulation of quantum system can be monitored and corrected on the fly

The field of quantum computation has seen tremendous progress in recent years. Bit by bit, quantum devices start to challenge conventional computers, at least...

Im Focus: Nanorobots propel through the eye

Scientists developed specially coated nanometer-sized vehicles that can be actively moved through dense tissue like the vitreous of the eye. So far, the transport of nano-vehicles has only been demonstrated in model systems or biological fluids, but not in real tissue. The work was published in the journal Science Advances and constitutes one step further towards nanorobots becoming minimally-invasive tools for precisely delivering medicine to where it is needed.

Researchers of the “Micro, Nano and Molecular Systems” Lab at the Max Planck Institute for Intelligent Systems in Stuttgart, together with an international...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

“3rd Conference on Laser Polishing – LaP 2018” Attracts International Experts and Users

09.11.2018 | Event News

On the brain’s ability to find the right direction

06.11.2018 | Event News

European Space Talks: Weltraumschrott – eine Gefahr für die Gesellschaft?

23.10.2018 | Event News

 
Latest News

In focus: Peptides, the “little brothers and sisters” of proteins

12.11.2018 | Life Sciences

Materials scientist creates fabric alternative to batteries for wearable devices

12.11.2018 | Materials Sciences

A two-atom quantum duet

12.11.2018 | Physics and Astronomy

VideoLinks
Science & Research
Overview of more VideoLinks >>>