Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Cellular defense against fatal associations between proteins and DNA

04.07.2014

DNA - the carrier of genetic information - is constantly threatened by damage originating from exogenous and endogenous sources.

Very special DNA lesions are DNA-protein crosslinks (DPCs) - proteins covalently linked to DNA. So far hardly anything was known about repair mechanisms specifically targeting DPCs.


Formaldehyde can crosslink DNA to proteins, which interferes with DNA replication. The protein Wss1 chops down the protein component of these crosslinks, thus enabling cells to complete replication.

Illustration: Stefan Jentsch / Copyright: MPI of Biochemistry

Stefan Jentsch’s team at the Max Planck Institute of Biochemistry (MPIB) in Martinsried, Germany, now discovered a protease that is able to chop down the protein component of DPCs, thereby enabling organisms to copy their genetic information even if DPCs arise. The results of this study have major implications for the understanding of genome integrity and cancer development.

The DNA in each cell is highly vulnerable to various types of damage. A special class of damage is caused by reactive compounds, such as formaldehyde, which are produced as byproducts of cellular reactions and cause the crosslinking (a formation of a covalent linkage) of proteins to DNA.

Importantly, these so-called DNA-protein crosslinks (DPCs) are also caused by several anti-cancer drugs and are extremely toxic as they interfere with essential processes such as DNA replication.

Cells need to unwind and separate the DNA double helix in order to copy its genetic information prior to the next round of cell division. DPCs inhibit this process by blocking the way of the unwinding enzyme (replicative helicase), thus preventing replication and consequently cell division.

In the laboratory of Stefan Jentsch at the MPIB, scientists now identified the protease Wss1 as a new safeguarding factor that chops down the protein components of DPCs and thereby enables cells to duplicate their genome. Julian Stingele, a PhD student in the laboratory, found that cells lacking Wss1 are particularly sensitive to formaldehyde, extremely vulnerable to DPCs and suffer from genomic instability.

Notably, Wss1 has the unique property to cleave proteins only in the presence of DNA, suggesting that the enzyme is well tailored for its task to remove DPCs from the genome and thus preserve genome stability.

Because the repair of DNA lesions is essential to prevent cancer formation, it is of crucial importance to understand the underlying cellular mechanisms. The newly identified DPC-repair pathway is particularly important for rapidly dividing cells. Given the fact that cancer cells divide much faster than the majority of human cells, Wss1 might be an attractive future drug target for cancer therapy.

Original Publication:
J. Stingele, M. Schwarz, N. Bloemeke, P. Wolf, and S. Jentsch: A DNA-dependent protease involved in DNA-protein crosslink repair. Cell, July 3, 2014.
DOI: 10.1016/j.cell.2014.04.053

Contact:
Prof. Dr. Stefan Jentsch
Molecular Cell Biology
Max Planck Institute of Biochemistry
Am Klopferspitz 18
82152 Martinsried
Germany
E-Mail: jentsch@biochem.mpg.de
http://www.biochem.mpg.de/jentsch

Anja Konschak
Public Relations
Max Planck Institute of Biochemistry
Am Klopferspitz 18
82152 Martinsried
Germany
Tel. +49 89 8578-2824
E-Mail: konschak@biochem.mpg.de
http://www.biochem.mpg.de/news

Weitere Informationen:

http://www.biochem.mpg.de/news/ueber_das_institut/forschungsbereiche/zellbiologi... - More Press Releases about the Research of Stefan Jentsch

Anja Konschak | Max-Planck-Institut

More articles from Life Sciences:

nachricht Scientists unlock ability to generate new sensory hair cells
22.02.2017 | Brigham and Women's Hospital

nachricht New insights into the information processing of motor neurons
22.02.2017 | Max Planck Florida Institute for Neuroscience

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Breakthrough with a chain of gold atoms

In the field of nanoscience, an international team of physicists with participants from Konstanz has achieved a breakthrough in understanding heat transport

In the field of nanoscience, an international team of physicists with participants from Konstanz has achieved a breakthrough in understanding heat transport

Im Focus: DNA repair: a new letter in the cell alphabet

Results reveal how discoveries may be hidden in scientific “blind spots”

Cells need to repair damaged DNA in our genes to prevent the development of cancer and other diseases. Our cells therefore activate and send “repair-proteins”...

Im Focus: Dresdner scientists print tomorrow’s world

The Fraunhofer IWS Dresden and Technische Universität Dresden inaugurated their jointly operated Center for Additive Manufacturing Dresden (AMCD) with a festive ceremony on February 7, 2017. Scientists from various disciplines perform research on materials, additive manufacturing processes and innovative technologies, which build up components in a layer by layer process. This technology opens up new horizons for component design and combinations of functions. For example during fabrication, electrical conductors and sensors are already able to be additively manufactured into components. They provide information about stress conditions of a product during operation.

The 3D-printing technology, or additive manufacturing as it is often called, has long made the step out of scientific research laboratories into industrial...

Im Focus: Mimicking nature's cellular architectures via 3-D printing

Research offers new level of control over the structure of 3-D printed materials

Nature does amazing things with limited design materials. Grass, for example, can support its own weight, resist strong wind loads, and recover after being...

Im Focus: Three Magnetic States for Each Hole

Nanometer-scale magnetic perforated grids could create new possibilities for computing. Together with international colleagues, scientists from the Helmholtz Zentrum Dresden-Rossendorf (HZDR) have shown how a cobalt grid can be reliably programmed at room temperature. In addition they discovered that for every hole ("antidot") three magnetic states can be configured. The results have been published in the journal "Scientific Reports".

Physicist Dr. Rantej Bali from the HZDR, together with scientists from Singapore and Australia, designed a special grid structure in a thin layer of cobalt in...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Booth and panel discussion – The Lindau Nobel Laureate Meetings at the AAAS 2017 Annual Meeting

13.02.2017 | Event News

Complex Loading versus Hidden Reserves

10.02.2017 | Event News

International Conference on Crystal Growth in Freiburg

09.02.2017 | Event News

 
Latest News

Prediction: More gas-giants will be found orbiting Sun-like stars

22.02.2017 | Physics and Astronomy

Researchers identify cause of hereditary skeletal muscle disorder

22.02.2017 | Health and Medicine

Positrons as a new tool for lithium ion battery research: Holes in the electrode

22.02.2017 | Power and Electrical Engineering

VideoLinks
B2B-VideoLinks
More VideoLinks >>>