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

• Published in: The Journal of biological chemistry Vol. 289; no. 16; pp. 10950 - 10957
• Main Authors: Slavoff, Sarah A., Heo, Jinho, Budnik, Bogdan A., Hanakahi, Leslyn A., Saghatelian, Alan
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 18.04.2014; American Society for Biochemistry and Molecular Biology
• Subjects: Cell Line; DNA Breaks, Double-Stranded; DNA End-Joining Repair - physiology; DNA Helicases - genetics; DNA Helicases - metabolism; DNA Repair; Humans; Ku Autoantigen; Open Reading Frames - physiology; Peptide Interactions; Peptides; Protein-Protein Interactions; Proteomics; Short ORF; Peptides; Peptide Interactions; DNA Repair; Proteomics; Short ORF; Protein-Protein Interactions
• ISSN: 0021-9258; 1083-351X; 1083-351X
• DOI: 10.1074/jbc.C113.533968

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. 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.