The human DDX52 protein is a nucleic acid helicase and strand annealase that promotes cell migration

DExD-box (DDX) proteins are essential for RNA metabolism and are targets for treatment of cancers and neurodevelopmental disorders. The biochemical mechanisms of many DDX proteins remain unclear, including human DDX52. DDX52 is essential for cell survival and is an emerging biomarker for the onset of metastatic melanoma. In this work, we identified that human DDX52 is an ATP-dependent translocase with 3'-5' polarity, which can unwind DNA duplexes and DNA/RNA hybrids. Further, DDX52 is a nucleic acid annealase, an activity that requires an N-terminal intrinsically disordered protein region. DDX52 becomes hyperactive at DNA annealing if DDX52 helicase activity is inactivated by mutagenesis. Using CRISPR-Cas9 genetic editing, we generated U2OS cell lines heterozygous for DDX52 (DDX52+/-), which exhibit growth defects and impaired cell migration, providing direct support for previous suggestions that DDX52 may promote cancer cell metastasis and C-myc regulation.