A Novel Role for the DNA Sensor IFI16 in the Cancer Cell Response to Chemotherapy

All cells must copy their DNA before dividing. Cancer cells divide rapidly, so tumours can be targeted by chemotherapies that interfere with DNA copying like Cisplatin. To copy DNA, the cell must open the two strands of the DNA helix to access the genetic code. Cisplatin forms a link between the DNA strands (called an ICL) so that they cannot be opened – this leads to damaged DNA, which kills the cancer cells. However, cells have specialised ways to remove ICLs, which cancer cells employ to resist the effects of treatment. 

We are working on a protein called IFI16, which evolved to identify DNA from invading viruses. We identify a new role for IFI16 in helping cancer cells deal with Cisplatin, and discovered that IFI16 binds to newly made DNA, and that IFI16 is modified after Cisplatin treatment which might partly explain how it functions in the cell. We are applying for funding to determine exactly how IFI16 limits Cisplatin-induced damage, and to test the importance of IFI16 modification. Knowing how cells repair chemotherapy-induced ICLs may lead to novel ways to target cancers, and identify which patients are likely to respond to particular drugs.