Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

New jigsaw piece for the repair of DNA crosslinks

27.05.2014

DNA damage repair is highly complex.

UZH researchers have now discovered another piece in the puzzle for the removal of extremely dangerous DNA lesions. Faithful and efficient repair of so-called crosslinks requires a collaboration between a specific signalling and repair protein. As crosslink-inducing agents are used in chemotherapy, the new insights are also important for the development of better anti-cancer treatment strategies.


Crosslink-inducing agents used in chemotherapy.

pictures:UZH

Environmental influences such as ionizing radiation, intense heat or various chemical substances damage the DNA constantly. Only thanks to efficient repair systems can mutations – changes in the DNA – largely be prevented. DNA crosslinks that covalently link both strands of the DNA double helix are among the most dangerous DNA lesions. Crosslinks block DNA replication and can thus cause cell death.

Moreover, their faulty repair can trigger the development of tumors. Crosslink repair is highly complex and only vaguely understood today. A team of cancer researchers headed by Alessandro Sartori from the University of Zurich now reveals interesting details as to how cells recognize crosslink damage. In their study recently published in Cell Reports, the scientists demonstrate that the interplay between two specific proteins is crucial for the flawless repair of crosslink damage.

Repair protein recognizes crosslink damage with the aid of a signal protein

For their study, the researchers examined the Fanconi anemia signal pathway, which coordinates the complex repair of crosslinks, with the aid of genetically modified and unchanged cells. Sartori and his team wanted to find out whether and how the signal pathway and the repair protein CtIP interact with one another. “We are able to show that CtIP recognizes and repairs crosslinks efficiently with the aid of the Fanconi anemia signal pathway, or FANCD2 to be more precise,” explains Sartori.

The scientists also discovered the point where CtIP attaches itself to the FANCD2 protein. According to the researchers, the interplay between the two proteins is necessary for the flawless and smooth repair of crosslink damage as it prevents the relocation of entire chromosome sections to another position (see figure). Referred to as chromosomal translocation, the process is one of the main causes of the development of cancer.

These days, substances that specifically trigger crosslink damage are used in cancer chemotherapy. The new findings are therefore important for both our understanding of the development of cancer and the further development of improved drugs.

Literature:
Olga Murina, Christine von Aesch, Ufuk Karakus, Lorenza P. Ferretti, Hella A. Bolck, Kay Hänggi, and Alessandro A. Sartori. FANCD2 and CtIP Cooperate to Repair DNA Interstrand Crosslinks. Cell Reports (2014). May 1, 2014. http://dx.doi.org/10.1016/j.celrep.2014.03.069

Fanconi anemia
Fanconi anemia (FA) is a rare congenital disorder that was first described in 1927 by Guido Fanconi (1892­–1979), Professor of Pediatrics at the University of Zurich. Fanconi anemia is triggered by mutations in genes that regulate the repair of DNA crosslinks. Patients who suffer from Fanconi anemia display bone marrow failure already during childhood and have a risk of developing cancer that is about 1,000 times higher compared to healthy individuals. Only around a third of Fanconi anemia patients live beyond the age of 30.

Weitere Informationen:

http://www.mediadesk.uzh.ch

Bettina Jakob | Universität Zürich

Further reports about: DNA FANCD2 anemia chemotherapy damage dangerous discovered mutations pathway proteins repair strategies substances

More articles from Life Sciences:

nachricht New Model of T Cell Activation
27.05.2016 | Albert-Ludwigs-Universität Freiburg im Breisgau

nachricht Fungi – a promising source of chemical diversity
27.05.2016 | Leibniz-Institut für Naturstoff-Forschung und Infektionsbiologie - Hans-Knöll-Institut (HKI)

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Worldwide Success of Tyrolean Wastewater Treatment Technology

A biological and energy-efficient process, developed and patented by the University of Innsbruck, converts nitrogen compounds in wastewater treatment facilities into harmless atmospheric nitrogen gas. This innovative technology is now being refined and marketed jointly with the United States’ DC Water and Sewer Authority (DC Water). The largest DEMON®-system in a wastewater treatment plant is currently being built in Washington, DC.

The DEMON®-system was developed and patented by the University of Innsbruck 11 years ago. Today this successful technology has been implemented in about 70...

Im Focus: Computational high-throughput screening finds hard magnets containing less rare earth elements

Permanent magnets are very important for technologies of the future like electromobility and renewable energy, and rare earth elements (REE) are necessary for their manufacture. The Fraunhofer Institute for Mechanics of Materials IWM in Freiburg, Germany, has now succeeded in identifying promising approaches and materials for new permanent magnets through use of an in-house simulation process based on high-throughput screening (HTS). The team was able to improve magnetic properties this way and at the same time replaced REE with elements that are less expensive and readily available. The results were published in the online technical journal “Scientific Reports”.

The starting point for IWM researchers Wolfgang Körner, Georg Krugel, and Christian Elsässer was a neodymium-iron-nitrogen compound based on a type of...

Im Focus: Atomic precision: technologies for the next-but-one generation of microchips

In the Beyond EUV project, the Fraunhofer Institutes for Laser Technology ILT in Aachen and for Applied Optics and Precision Engineering IOF in Jena are developing key technologies for the manufacture of a new generation of microchips using EUV radiation at a wavelength of 6.7 nm. The resulting structures are barely thicker than single atoms, and they make it possible to produce extremely integrated circuits for such items as wearables or mind-controlled prosthetic limbs.

In 1965 Gordon Moore formulated the law that came to be named after him, which states that the complexity of integrated circuits doubles every one to two...

Im Focus: Researchers demonstrate size quantization of Dirac fermions in graphene

Characterization of high-quality material reveals important details relevant to next generation nanoelectronic devices

Quantum mechanics is the field of physics governing the behavior of things on atomic scales, where things work very differently from our everyday world.

Im Focus: Graphene: A quantum of current

When current comes in discrete packages: Viennese scientists unravel the quantum properties of the carbon material graphene

In 2010 the Nobel Prize in physics was awarded for the discovery of the exceptional material graphene, which consists of a single layer of carbon atoms...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Networking 4.0: International Laser Technology Congress AKL’16 Shows New Ways of Cooperations

24.05.2016 | Event News

Challenges of rural labor markets

20.05.2016 | Event News

International expert meeting “Health Business Connect” in France

19.05.2016 | Event News

 
Latest News

11 million Euros for research into magnetic field sensors for medical diagnostics

27.05.2016 | Awards Funding

Fungi – a promising source of chemical diversity

27.05.2016 | Life Sciences

New Model of T Cell Activation

27.05.2016 | Life Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>