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New protein involved in defense mechanism against cancer

March 31, 2017

The surprising finding of this study, presented in the scientific journal Nature Structural & Molecular Biology, is not only the identity of the new player but also how it is doing the job. By following proteins in cells with DNA damage, the researchers found that the VCP/p97 complex is among the proteins that are being recruited to DNA damage. This was unanticipated since VCP/p97 is known to be primarily involved in the destruction of defective proteins. VCP/p97 is doing this by unwinding them so that the waste proteins can be chopped in pieces by dedicated enzymes. This important function also explains its involvement in a type of familial dementia and ALS since this kind of waste proteins typically pile up in these diseases.

It turns out that VCP/p97 is doing something similar at damaged DNA although with a very different outcome. The work shows that VCP/p97 facilitates the binding of 53BP1 by removing a protein that occupies the places where 53BP1 can bind. So instead of unwinding a protein to prepare it for destruction, VCP/p97 pulls a protein out of the way for 53BP1. The researchers also show that worms that have less of this complex are very sensitive to DNA damage supporting an important and evolutionary conserved role of VCP/p97 in DNA damage control. This new mechanism of recruiting a protein by removing another one that gets in the way sheds new light onto how the tumor suppressor 53BP1 finds damaged DNA. An important question that remains is if VCP/p97 plays similar roles in other processes.

Source Karolinska Institutet