In human cells, DNA occurs only in the cell nucleus as the carrier of genetic information. In order to protect it, specialized proteins regularly scan the individual strands for defects, and repair them. One example of this is the protein Rad50, a DNA sensor that binds to DNA and detects defective sites. A team of scientists headed by Prof. Jrgen Ruland of the TUM together with colleagues from the LMU have now discovered another important task performed by Rad50.
There is normally no DNA in the cytoplasm surrounding the cell nucleus. However, if any does turn up there, it is frequently foreign DNA from a virus, for instance, that has infected the cell. Just like humans, some types of viruses use DNA to carry their genetic information. Thus the innate immune system has developed alarm mechanisms to detect foreign DNA in cytoplasm quickly and effectively, and activate the immune system by producing messenger substances.
However, it remains largely unclear just how this activation process occurs in the cytoplasm. In their study, lead author Dr. Susanne Roth and her colleagues have now shown that the DNA sensor Rad50 from the cell nucleus is also an important trigger for antiviral defense. "It is very surprising even for us that Rad50, which specializes in DNA in the cell nucleus, also detects foreign viral DNA and acts as a connecting link for the corresponding immune response", says Prof. Jrgen Ruland, explaining the significance of the findings.
One protein - two functions
In their experiments, the participating scientists infected immune cells with a virus that introduced its DNA into the cytoplasm. They were able to show that Rad50 bound to the viral DNA in the cytoplasm, even though it normally docks onto damaged DNA in the cell nucleus. A crucial factor was that Rad50 interacted with a specific signal protein (CARD9) of the immune system at the same time, forming a complex. The researchers succeeded in demonstrating this
|Contact: Vera Siegler|
Technische Universitaet Muenchen