The DNA is being damaged continuously: It is affected by solar UV radiation just as by toxic substances from the environment. However, defects also occur during cell division: For this, the DNA has to be doubled and during this complex process defects occur occasionally.
On principle, the organism is able to repair such damages on its own, even serious damages like complete DNA double-strand breaks at the same site. In this case, first the so-called MRN protein complex is called into action: By means of this complex, the damage is detected and signaled to the repair system of the cell.
Important protein complex does not work properly
In the case of the young woman, this important protein complex does not work properly. The scientists are familiar with the complex: It consists of three proteins. For two of them, mutations are known for years. The newly discovered defect concerns the third protein which is referred to as RAD50 and which holds the ends of the DNA break together like a molecular clamp.
"We know the patient and her parents for almost 15 years now" says Prof. Detlev Schindler of the Institute for Human Genetics of the University of Würzburg. At the beginning, the scientists assumed that the girl was suffering from the so-called Nijmegen breakage syndrome (NBS). This congenital disease results from one of the defects of the protein complex known at that time. It is very rare and, statistically speaking, it only affects one in three million people.
Patient not affected by serious complications
The young woman shows symptoms that are typical for this disease: microcephaly, growth retardation as well as physical and mental retardation. In the course of time, it turned out that something was different with that woman, because she was not affected by the serious complications of the disease. She never experienced serious respiratory infections which very often are fatal for NBS patients. Her immune defence is normal. To date, she shows no signs of lymph gland cancer.
Now, the reason for those deviations has been found: The patient does not suffer from NBS, but from a disease which has been unknown so far. The scientists called it "NBS-like disorder". The mutation on which the disease is based has been characterized by the researchers from Würzburg in cooperation with colleagues from Hanover, Magdeburg, Berlin, Israel and Australia.
The woman's organism does not form enough RAD50 proteins. Moreover, the residual proteins do not execute their function sufficiently. "There are a residual quantity and a residual function, and possibly this is the only reason why the patient is still alive", says Detlev Schindler. Because if no RAD50 is available at all for an organism, it dies already as an embryo. This is known from mice showing the defect mentioned above. Perhaps the patient's mutation is so rare that she is one of only few living people suffering from this disease.
Benefits of the findings
What are the benefits of these findings? The patient herself cannot benefit from the findings. However, perhaps they might be helpful for the parents of children for whom there is a suspicion of having the Nijmegen breakage syndrome. Because now, by means of genetic diagnostics it is possible to verify whether they are really suffering from this serious syndrome or from the newly discovered disease.
The research results also offer benefits for science. "We have clarified another step going on during the repair of DNA double-strand breaks and we begin to understand which role it plays", says the professor from Würzburg. Currently, he and his team examine how the RAD50 protein works together with other proteins. This work shall provide further findings concerning the signaling pathways within the cell allowing the organism to eliminate damages of the genetic material.
For further information
Professor Detlev Schindler, Phone ++49 (931) 31-88075, firstname.lastname@example.org
"Human RAD50 Deficiency in a Nijmegen Breakage Syndrome-like Disorder", Regina Waltes, Reinhard Kalb, Magtouf Gatei, Amanda Kijas, Markus Stumm, Alexandra Sobeck, Britta Wieland, Raymonda Varon, Yaniv Lerenthal, Martin F. Lavin, Detlev Schindler, and Thilo Dörk, The American Journal of Human Genetics (2009), doi: 10.1016/j.ajhg.2009.04.010
Robert Emmerich | idw
Further reports about: > DNA > DNA double-strand breaks > Human Genetics > Human vaccine > NBS > NBS-like disorder > New Disease > Nijmegen breakage syndrome > RAD50 > cell division > congenital disease > genetic material > lymph gland cancer > mental retardation > microcephaly > process defects > respiratory infection > solar UV radiation > toxic substance > toxic substances from the environment
Novel mechanisms of action discovered for the skin cancer medication Imiquimod
21.10.2016 | Technische Universität München
Second research flight into zero gravity
21.10.2016 | Universität Zürich
Researchers from the Institute for Quantum Computing (IQC) at the University of Waterloo led the development of a new extensible wiring technique capable of controlling superconducting quantum bits, representing a significant step towards to the realization of a scalable quantum computer.
"The quantum socket is a wiring method that uses three-dimensional wires based on spring-loaded pins to address individual qubits," said Jeremy Béjanin, a PhD...
In a paper in Scientific Reports, a research team at Worcester Polytechnic Institute describes a novel light-activated phenomenon that could become the basis for applications as diverse as microscopic robotic grippers and more efficient solar cells.
A research team at Worcester Polytechnic Institute (WPI) has developed a revolutionary, light-activated semiconductor nanocomposite material that can be used...
By forcefully embedding two silicon atoms in a diamond matrix, Sandia researchers have demonstrated for the first time on a single chip all the components needed to create a quantum bridge to link quantum computers together.
"People have already built small quantum computers," says Sandia researcher Ryan Camacho. "Maybe the first useful one won't be a single giant quantum computer...
COMPAMED has become the leading international marketplace for suppliers of medical manufacturing. The trade fair, which takes place every November and is co-located to MEDICA in Dusseldorf, has been steadily growing over the past years and shows that medical technology remains a rapidly growing market.
In 2016, the joint pavilion by the IVAM Microtechnology Network, the Product Market “High-tech for Medical Devices”, will be located in Hall 8a again and will...
'Ferroelectric' materials can switch between different states of electrical polarization in response to an external electric field. This flexibility means they show promise for many applications, for example in electronic devices and computer memory. Current ferroelectric materials are highly valued for their thermal and chemical stability and rapid electro-mechanical responses, but creating a material that is scalable down to the tiny sizes needed for technologies like silicon-based semiconductors (Si-based CMOS) has proven challenging.
Now, Hiroshi Funakubo and co-workers at the Tokyo Institute of Technology, in collaboration with researchers across Japan, have conducted experiments to...
14.10.2016 | Event News
14.10.2016 | Event News
12.10.2016 | Event News
21.10.2016 | Health and Medicine
21.10.2016 | Information Technology
21.10.2016 | Materials Sciences