Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Chromosomes: the importance of keeping the balance

17.02.2016

The genetic material of cancer cells is unstable. For example, the number of chromosomes, which are the individual elements of packed DNA, is changed in so called aneuploidies. This imbalance in chromosomes, which often occurs early in tumor development, leads to cell stress and promotes disease. How this can happen is now shown by the discovery of a research team led by Zuzana Storchová at the Max Planck Institute of Biochemistry in Martinsried, reported in a groundbreaking study published in Nature Communications. An imbalance in an enzyme called MCM2-7 that is essential for DNA replication is likely to be responsible for this escalating genomic instability.

Before every cell division, the hereditary information, that is the chromosomes, are duplicated and distributed to the daughter cells so that each cell again carries its species-specific number of chromosomes, which is 46 in humans.


Many cancer cells are aneuploid. It means, that they have more or less chromosomes than usual. The changed number of chromosomes (pink) leads to a higher rate of DNA-damage.

V. Passerini © MPI of Biochemistry

„Mistakes can occur at any time during the process of cell division“, explains Zuzana Storchová, the head of the Genome Stability research group. „The chromosomes can be divided unequally and in this way one human cell carries 47 chromosomes while the other carries 45 chromosomes“.

It is known that chromosome imbalance, called aneuploidy, often occurs early in the development of cancer. Aneuploidy probably even appears before the much-feared gene mutations, which are thought to be the cause of cancer. „We wanted to know whether a change in the number of chromosomes directly contributes to gene mutations”, explains Storchová.

To answer this question, the researchers took advantage of a method that has until now been successfully used by only a small number of research groups worldwide: chromosome transfer. In a first step, single chromosomes are isolated and then transferred to recipient cells. The specific effects of aneuploidy can be deciphered in detail by directly comparing with identical cells that do not carry the extra chromosome.

To get a detailed understanding of the changes in the genome of aneuploid cells, the researchers teamed up with the group of Batsheva Kerem from the University of Jerusalem and the group of Wigard Kloosterman from the University Medical Center in Utrecht. In fact, Storchova’s team and their collaborators observed that aneuploid cells exhibited a clearly elevated rate of DNA damage as well as an enhanced level of DNA rearrangements.

„We see that an imbalance in chromosome numbers has serious consequences, because the chromosomes contain genes, which are the construction manuals for all the different proteins inside a cell. Proteins are the executors of a vast array of important cellular functions and operate like little molecular machines“, explains Verena Passerini from Storchova‘s team and the first author of the study.

„If there are too many or too few chromosomes, inside a cell, then there will be a corresponding increase or decrease in the amount of proteins that are made. This probably causes cell stress and leads to cellular damage“. In this way, the whole cellular system loses its balance.

The researchers could also identify a responsible factor: The MCM2-7 protein complex that is essential for DNA replication during cell division. In the aneuploid cells there was less MCM2-7 present than normal. The reduced levels of MCM2-7 impair DNA replication, which in turn leads to chromosomal rearrangements and mutations. These defects could be partially corrected by increasing the levels of MCM2-7.

„We could now show for the first time what profound effects aneuploidy can have on important cellular functions: An alteration in chromosome number causes stress during DNA replication, which leads to genetic instability“, summarizes Storchová.

It is now clear that certain defects that appear at the beginning of tumor development, such as aneuploidy, promote further damage in their wake. „It has been very difficult to understand the early stages of tumor development", says Storchová. „Our aneuploid cells represent a new model system for processes that drive cancer development."

Original publication:
V. Passerini, E. Ozeri-Galai, M. S. de Pagter, N. Donnelly, S. Schmalbrock, W. P. Kloosterman, B. Kerem, Z. Storchová: The presence of extra chromosomes leads to genomic instability, Nature Communications, February 2016
DOI: 10.1038/NCOMMS10754

Contact:
Dr. Zuzana Storchová
Maintenance of Genome Stability
Max-Planck-Institut für Biochemie
Am Klopferspitz 18
82152 Martinsried
E-Mail: storchov@biochem.mpg.de
www.biochem.mpg.de/storchova

Dr. Christiane Menzfeld
Public Relations
Max Planck Institute of Biochemistry
Am Klopferspitz 18
82152 Martinsried
Germany
Tel. +49 89 8578-2824
E-Mail: pr@biochem.mpg.de

www.biochem.mpg.de 

Weitere Informationen:

http://www.biochem.mpg.de/en/news - More press releases of the MPI of Biochemistry
http://www.biochem.mpg.de/storchova - Website of the Research Group "Maintenance of Genome Stability" (Zuzana Storchova)

Dr. Christiane Menzfeld | Max-Planck-Institut für Biochemie

More articles from Life Sciences:

nachricht The birth of a new protein
20.10.2017 | University of Arizona

nachricht Building New Moss Factories
20.10.2017 | 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: Neutron star merger directly observed for the first time

University of Maryland researchers contribute to historic detection of gravitational waves and light created by event

On August 17, 2017, at 12:41:04 UTC, scientists made the first direct observation of a merger between two neutron stars--the dense, collapsed cores that remain...

Im Focus: Breaking: the first light from two neutron stars merging

Seven new papers describe the first-ever detection of light from a gravitational wave source. The event, caused by two neutron stars colliding and merging together, was dubbed GW170817 because it sent ripples through space-time that reached Earth on 2017 August 17. Around the world, hundreds of excited astronomers mobilized quickly and were able to observe the event using numerous telescopes, providing a wealth of new data.

Previous detections of gravitational waves have all involved the merger of two black holes, a feat that won the 2017 Nobel Prize in Physics earlier this month....

Im Focus: Smart sensors for efficient processes

Material defects in end products can quickly result in failures in many areas of industry, and have a massive impact on the safe use of their products. This is why, in the field of quality assurance, intelligent, nondestructive sensor systems play a key role. They allow testing components and parts in a rapid and cost-efficient manner without destroying the actual product or changing its surface. Experts from the Fraunhofer IZFP in Saarbrücken will be presenting two exhibits at the Blechexpo in Stuttgart from 7–10 November 2017 that allow fast, reliable, and automated characterization of materials and detection of defects (Hall 5, Booth 5306).

When quality testing uses time-consuming destructive test methods, it can result in enormous costs due to damaging or destroying the products. And given that...

Im Focus: Cold molecules on collision course

Using a new cooling technique MPQ scientists succeed at observing collisions in a dense beam of cold and slow dipolar molecules.

How do chemical reactions proceed at extremely low temperatures? The answer requires the investigation of molecular samples that are cold, dense, and slow at...

Im Focus: Shrinking the proton again!

Scientists from the Max Planck Institute of Quantum Optics, using high precision laser spectroscopy of atomic hydrogen, confirm the surprisingly small value of the proton radius determined from muonic hydrogen.

It was one of the breakthroughs of the year 2010: Laser spectroscopy of muonic hydrogen resulted in a value for the proton charge radius that was significantly...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

ASEAN Member States discuss the future role of renewable energy

17.10.2017 | Event News

World Health Summit 2017: International experts set the course for the future of Global Health

10.10.2017 | Event News

Climate Engineering Conference 2017 Opens in Berlin

10.10.2017 | Event News

 
Latest News

Terahertz spectroscopy goes nano

20.10.2017 | Information Technology

Strange but true: Turning a material upside down can sometimes make it softer

20.10.2017 | Materials Sciences

NRL clarifies valley polarization for electronic and optoelectronic technologies

20.10.2017 | Interdisciplinary Research

VideoLinks
B2B-VideoLinks
More VideoLinks >>>