A role for DEAD box 1 at DNA double-strand breaks.

DEAD box proteins are a family of putative RNA helicases associated with all aspects of cellular metabolism involving the modification of RNA secondary structure. DDX1 is a member of the DEAD box protein family that is overexpressed in a subset of retinoblastoma and neuroblastoma cell lines and tumors. DDX1 is ...
found primarily in the nucleus, where it forms two to four large aggregates called DDX1 bodies. Here, we report a rapid redistribution of DDX1 in cells exposed to ionizing radiation, resulting in the formation of numerous foci that colocalize with gamma-H2AX and phosphorylated ATM foci at sites of DNA double-strand breaks (DSBs). The formation of DDX1 ionizing-radiation-induced foci (IRIF) is dependent on ATM, which was shown to phosphorylate DDX1 both in vitro and in vivo. The treatment of cells with RNase H prevented the formation of DDX1 IRIF, suggesting that DDX1 is recruited to sites of DNA damage containing RNA-DNA structures. We have shown that DDX1 has RNase activity toward single-stranded RNA, as well as ADP-dependent RNA-DNA- and RNA-RNA-unwinding activities. We propose that DDX1 plays an RNA clearance role at DSB sites, thereby facilitating the template-guided repair of transcriptionally active regions of the genome.
Mesh Terms:
Cell Cycle Proteins, Cell Line, DEAD-box RNA Helicases, DNA Breaks, Double-Stranded, DNA-Activated Protein Kinase, DNA-Binding Proteins, Gamma Rays, Histones, Humans, Immunoprecipitation, Nuclear Proteins, Nucleic Acid Heteroduplexes, Phosphorylation, Protein-Serine-Threonine Kinases, RNA, Ribonuclease H, Transcription, Genetic, Tumor Suppressor Proteins
Mol. Cell. Biol.
Date: Oct. 01, 2008
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