May 28, 2014
New Jigsaw Piece For The Repair Of DNA Crosslinks
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.
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.