Research Group "Molecular Mechanisms of DNA Repair" (Christian Biertümpfel)
Our DNA is constantly under attack: It is relentlessly exposed to hazardous influences such as high-energy radiation, ultraviolet rays or toxic chemicals. Because DNA damage can lead to serious diseases like cancer or cause birth defects, cells try to repair damage as soon as possible. Together with his research group “Molecular Mechanisms of DNA Repair”, Christian Biertümpfel is seeking to identify the factors involved and to elucidate how they are regulated and interact with each other.
A double-strand break with a completely severed DNA molecule is considered to be particularly dangerous and poses two risks at the same time: If the damage cannot be repaired, a cell is forced to destroy itself through programmed cell suicide, also known as apoptosis. On the other hand, if the damage is repaired incorrectly, massive alterations can remain in the DNA – a characteristic of cancer and other disorders. Biertümpfel is therefore interested in a specific cellular repair mechanism implemented in double-strand breaks that is generally error-free: homologous recombination.
This process controls the exchange of DNA segments and thus ensures genetic variance in the offspring during sperm and egg development. The repair is made possible through homologous recombination, because in higher organisms genetic information exists in duplicate. If one copy is damaged, the second copy can serve as a template for the repair.
During the repair process a structure called Holliday junction is formed: Intact and damaged DNA strands are intertwined in a “molecular knot”. Based on the undamaged strand, the damage in the defective DNA molecule can be repaired. Once the repair has been completed, the Holliday junction is resolved so that once again two functional DNA molecules exist. Biertümpfel would like to investigate this critical and extremely complex cellular process.
In the long term he and his team want to decipher the entire modular network of DNA repair as well as its regulation and cellular links. This ambitious project includes a poorly understood mechanism which only comes into play when the normal DNA repair capacity reaches its limits: If the damage proves to be irreparable, it is initially accepted. At the next DNA replication an intact piece of DNA is synthesized and used to replace the defective segment. This process plays an important role in dealing with DNA damage that is caused by ultraviolet rays from the sun, which can lead to skin cancer.