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 Show me your leaves - Health check for urban trees
12.12.2017 | Gesellschaft für Ökologie e.V.

nachricht Liver Cancer: Lipid Synthesis Promotes Tumor Formation
12.12.2017 | Universität Basel

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Scientists channel graphene to understand filtration and ion transport into cells

Tiny pores at a cell's entryway act as miniature bouncers, letting in some electrically charged atoms--ions--but blocking others. Operating as exquisitely sensitive filters, these "ion channels" play a critical role in biological functions such as muscle contraction and the firing of brain cells.

To rapidly transport the right ions through the cell membrane, the tiny channels rely on a complex interplay between the ions and surrounding molecules,...

Im Focus: Towards data storage at the single molecule level

The miniaturization of the current technology of storage media is hindered by fundamental limits of quantum mechanics. A new approach consists in using so-called spin-crossover molecules as the smallest possible storage unit. Similar to normal hard drives, these special molecules can save information via their magnetic state. A research team from Kiel University has now managed to successfully place a new class of spin-crossover molecules onto a surface and to improve the molecule’s storage capacity. The storage density of conventional hard drives could therefore theoretically be increased by more than one hundred fold. The study has been published in the scientific journal Nano Letters.

Over the past few years, the building blocks of storage media have gotten ever smaller. But further miniaturization of the current technology is hindered by...

Im Focus: Successful Mechanical Testing of Nanowires

With innovative experiments, researchers at the Helmholtz-Zentrums Geesthacht and the Technical University Hamburg unravel why tiny metallic structures are extremely strong

Light-weight and simultaneously strong – porous metallic nanomaterials promise interesting applications as, for instance, for future aeroplanes with enhanced...

Im Focus: Virtual Reality for Bacteria

An interdisciplinary group of researchers interfaced individual bacteria with a computer to build a hybrid bio-digital circuit - Study published in Nature Communications

Scientists at the Institute of Science and Technology Austria (IST Austria) have managed to control the behavior of individual bacteria by connecting them to a...

Im Focus: A space-time sensor for light-matter interactions

Physicists in the Laboratory for Attosecond Physics (run jointly by LMU Munich and the Max Planck Institute for Quantum Optics) have developed an attosecond electron microscope that allows them to visualize the dispersion of light in time and space, and observe the motions of electrons in atoms.

The most basic of all physical interactions in nature is that between light and matter. This interaction takes place in attosecond times (i.e. billionths of a...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

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

AKL’18: The opportunities and challenges of digitalization in the laser industry

07.12.2017 | Event News

 
Latest News

Hot vibrating gases under the electron spotlight

12.12.2017 | Life Sciences

New silicon structure opens the gate to quantum computers

12.12.2017 | Information Technology

Using drones to estimate crop damage by wild boars

12.12.2017 | Ecology, The Environment and Conservation

VideoLinks
B2B-VideoLinks
More VideoLinks >>>