IFI16-HIN200 is an RPA-like ssDNA-binding domain

Interferon-y Inducible protein 16 (IFI16) belongs to a family of transcriptional repressors and tumour suppressors that are inducible by interferons. Each family member contains at most two 200 amino-acid domains of unknown function called HIN200. IFI16 may have DNA repair function since it becomes a component of the DNA repair multi-protein complex known as the BASC complex after UV-induced DNA damage. Using bioinformatics methods, we predicted that the IFI16-HIN200 domain has the characteristic fold of Replication Protein A (RPA), a single-stranded nucleic acid binding protein that removes nucleic acid secondary structures during DNA replication and repair. To further functionally verify the predicted fold, I show by biochemical and biophysical approaches that IFI16-HIN200 has most of RPA nucleic acid binding properties since it recognizes ssDNA in the same orientation as RPA, oligomerizes upon ssDNA binding, wraps and stretches ssDNA, but does not destabilize dsDNA.