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.
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.
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 (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.
Bettina Jakob | Universität Zürich
Transport of molecular motors into cilia
28.03.2017 | Aarhus University
Asian dust providing key nutrients for California's giant sequoias
28.03.2017 | University of California - Riverside
The Institute of Semiconductor Technology and the Institute of Physical and Theoretical Chemistry, both members of the Laboratory for Emerging Nanometrology (LENA), at Technische Universität Braunschweig are partners in a new European research project entitled ChipScope, which aims to develop a completely new and extremely small optical microscope capable of observing the interior of living cells in real time. A consortium of 7 partners from 5 countries will tackle this issue with very ambitious objectives during a four-year research program.
To demonstrate the usefulness of this new scientific tool, at the end of the project the developed chip-sized microscope will be used to observe in real-time...
Astronomers from Bonn and Tautenburg in Thuringia (Germany) used the 100-m radio telescope at Effelsberg to observe several galaxy clusters. At the edges of these large accumulations of dark matter, stellar systems (galaxies), hot gas, and charged particles, they found magnetic fields that are exceptionally ordered over distances of many million light years. This makes them the most extended magnetic fields in the universe known so far.
The results will be published on March 22 in the journal „Astronomy & Astrophysics“.
Galaxy clusters are the largest gravitationally bound structures in the universe. With a typical extent of about 10 million light years, i.e. 100 times the...
Researchers at the Goethe University Frankfurt, together with partners from the University of Tübingen in Germany and Queen Mary University as well as Francis Crick Institute from London (UK) have developed a novel technology to decipher the secret ubiquitin code.
Ubiquitin is a small protein that can be linked to other cellular proteins, thereby controlling and modulating their functions. The attachment occurs in many...
In the eternal search for next generation high-efficiency solar cells and LEDs, scientists at Los Alamos National Laboratory and their partners are creating...
Silicon nanosheets are thin, two-dimensional layers with exceptional optoelectronic properties very similar to those of graphene. Albeit, the nanosheets are less stable. Now researchers at the Technical University of Munich (TUM) have, for the first time ever, produced a composite material combining silicon nanosheets and a polymer that is both UV-resistant and easy to process. This brings the scientists a significant step closer to industrial applications like flexible displays and photosensors.
Silicon nanosheets are thin, two-dimensional layers with exceptional optoelectronic properties very similar to those of graphene. Albeit, the nanosheets are...
20.03.2017 | Event News
14.03.2017 | Event News
07.03.2017 | Event News
29.03.2017 | Materials Sciences
29.03.2017 | Physics and Astronomy
29.03.2017 | Earth Sciences