Characterizing the role of DDX3X in DNA double strand break repair; Implications for lymphocyte biology

Abstract

DDX3X is a human, ATP-dependent RNA helicase with roles throughout RNA metabolism. A number of human diseases are associated with alterations in this gene, particularly in hematological malignancies. We aimed to investigate a novel function for DDX3X in DNA double-strand break (DSB) repair and its role in lymphocyte biology. We confirmed a traditional role for DDX3X in regulating DNA DSB repair protein levels, and herein provide evidence for a novel role as an active participant in DSB repair. We propose that DDX3X is recruited to DSBs in actively transcribed regions to regulate DSB-induced RNA metabolism. Finally, we developed CRISPR/Cas9 techniques to interrogate the function of DDX3X, and its Y-homologue, in lymphocyte biology. Thus, DDX3X plays an important role in DSB repair likely consequential to lymphocyte health and disease.