In order to understand the process better, the researchers then asked which regions of the CtIP protein are involved in binding it to the broken DNA ends. By testing small portions of the protein, they found that a region in the central part of CtIP helps recruit the protein. They named this region the "damage recruitment" (DR) domain.

Further studies suggested that the DR domain within CtIP is normally hidden inside the folded protein. Only when the cell sends a DNA damage signal is CtIP's DR domain exposed, and only then can CtIP bind to the broken DNA. In this way, CtIP is like a switchblade that cells open only in the presence of DNA damage.

The authors believe that exposure of CtIP 's DR domain and its recruitment to the site of DNA damage triggers a chain reaction that results in DNA repair, and they now want to understand exactly what CtIP does to start the DNA repair process.

You is also trying to understand the modifications in CtIP that cause the DR domain to be exposed, and is looking into the role of CtIP in cancer. "Mutations in CtIP have not been mapped extensively in human tumors, but from this data, we predict that mutations to the DR domain would lead to cancer," he says.

In the long term, the team hopes that a better understanding of the DNA damage pathway may provide clues for cancer treatment in the future. "CtIP is another important player in the double-strand break response," says Hunter. "We have added another piece to the complex puzzle of DNA repair."

Source: Salk Institute