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Mol. Cell. Biol. doi:10.1128/MCB.01053-08
Copyright (c) 2008, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

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

Department of Oncology, University of Alberta and Cross Cancer Institute, 11560 University Avenue, Edmonton, Alberta T6G 1Z2 Canada

^* To whom correspondence should be addressed. Email: roseline{at}cancerboard.ab.ca.

	Abstract

DEAD box proteins are a family of putative RNA helicases involved in all aspects of cellular metabolism involving modification of RNA secondary structure. DDX1 is a member of the DEAD box protein family that is over-expressed in a subset of retinoblastoma and neuroblastoma cell lines and tumors. DDX1 is primarily found in the nucleus where it forms 2 to 4 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 co-localize with -H2AX and phosphorylated ATM foci at sites of DNA double-strand breaks. Formation of DDX1 ionizing radiation-induced foci (IRIF) is dependent on ATM which was shown to phosphorylate DDX1 both in vitro and in vivo. 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 show that DDX1 has single-stranded ribonuclease activity 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 template-guided repair of transcriptionally active regions of the genome.