The interferon-inducible protein 16 is a single-stranded nucleic acid binding protein with unwinding and endonuclease activities

IFI16 belongs to a protein family (HIN200) that contains a characteristic 200-amino-acid protein domain with unknown function. Members of this family were initially described as transcriptional regulators but IFI16 is also involved in other processes such as DNA repair and programmed cell death. To gain further insights into the biochemical mechanisms underlying these functions we made bioinformatics predictions followed by biochemical validation. We predicted and verified experimentally that the 200-amino-acid domain of IFI16 is structurally and functionally similar to replication protein A (RPA), a protein that removes secondary structure on single-stranded DNA during DNA replication and repair. In addition, I found that IFI16 can unwind double-stranded DNA and has an endonuclease activity. This later unexpected discovery reveals a new function for IFI16. Finally, I further discuss the implications of this discovery in regard to the current knowledge about the function of this protein as well as new directions of studies.