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.
Li
Lei
L
Department of Oncology, University of Alberta, Edmonton, Alberta, Canada.
Monckton
Elizabeth A
EA
Godbout
Roseline
R
D064007:Ataxia Telangiectasia Mutated Proteins; D018797:Cell Cycle Proteins / Q000378:metabolism; D002460:Cell Line; D053487:DEAD-box RNA Helicases / Q000378:metabolism*; D053903:DNA Breaks, Double-Stranded / Q000187:drug effects / Q000528:radiation effects; D051747:DNA-Activated Protein Kinase / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism; D005720:Gamma Rays; D006657:Histones / Q000378:metabolism; D006801:Humans; D047468:Immunoprecipitation; D009687:Nuclear Proteins / Q000378:metabolism; D009692:Nucleic Acid Heteroduplexes / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects / Q000528:radiation effects; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D012313:RNA / Q000235:genetics; D016914:Ribonuclease H / Q000494:pharmacology; D014158:Transcription, Genetic / Q000187:drug effects / Q000528:radiation effects; D025521:Tumor Suppressor Proteins / Q000378:metabolism
D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; C468783:H2AX protein, human; D006657:Histones; D009687:Nuclear Proteins; D009692:Nucleic Acid Heteroduplexes; D025521:Tumor Suppressor Proteins; D012313:RNA; C576324:ATM protein, human; D064007:Ataxia Telangiectasia Mutated Proteins; D051747:DNA-Activated Protein Kinase; C497263:PRKDC protein, human; D017346:Protein Serine-Threonine Kinases; D016914:Ribonuclease H; C086252:DDX1 protein, human; D053487:DEAD-box RNA Helicases