A Human Short Open Reading Frame (sORF)-encoded Polypeptide That Stimulates DNA End Joining

Background: Large numbers of peptides encoded in human short open reading frames have been recently identified but not yet functionally characterized. Results: A peptide interacts with the Ku heterodimer and stimulates nonhomologous end-joining DNA repair. Conclusion: Newly discovered cellular peptides can be functionally characterized by identifying their interaction partners. Significance: Short ORF-encoded polypeptides participate in essential cellular processes.The recent discovery of numerous human short open reading frame (sORF)-encoded polypeptides (SEPs) has raised important questions about the functional roles of these molecules in cells. Here, we show that a 69-amino acid SEP, MRI-2, physically interacts with the Ku heterodimer to stimulate DNA double-strand break ligation via nonhomologous end joining. The characterization of MRI-2 suggests that this SEP may participate in DNA repair and underscores the potential of SEPs to serve important biological functions in mammalian cells.