title: Establishment of a Primary Screening Assay for the DHX9 Helicase.
abstract: The RNA helicase DHX9 is an ATP-dependent DExH box helicase that can unwind DNA and RNA. Much evidence has implicated DHX9 at multiple levels of gene expression regulation ranging from genome stability and replication, to transcriptional control and translation regulation. Its association with the EWS-FLI1 fusion product, as well as the finding that its suppression can be synthetic lethal with the BCL-2 family inhibitor ABT-737 indicates a potential role in tumor maintenance. Hence, to identify small molecules that could interfere with its activity, we developed a homogenous RNA-dependent ATPase assay. We show that aurintricarboxylic acid, a promiscuous protein-nucleic acid inhibitor prevents DHX9-mediated hydrolysis demonstrating that the assay is also capable of detecting compounds that impinge on DHX9:RNA association.
authors.forename: Regina
authors.initials: R
authors.lastname: Cencic
authors.forename: Patrick
authors.initials: P
authors.lastname: Senechal
authors.affiliation: Rm 810, 3655 Promenade Sir William Osler., McIntyre Medical Sciences Building, Montreal, Quebec, H3G 1Y6, Canada. jerry.pelletier@mcgill.ca.
authors.forename: Jerry
authors.initials: J
authors.lastname: Pelletier
mesh_terms: D053487:DEAD-box RNA Helicases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D057075:Enzyme Assays / Q000379:methods*; D006801:Humans; D009363:Neoplasm Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism
chemical_list: D009363:Neoplasm Proteins; D011994:Recombinant Proteins; C098487:DHX9 protein, human; D053487:DEAD-box RNA Helicases