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.
Keywords: ATPase assay, ATA, aurintricarboxylic acid, DHX9, HTS, RNA binding, RNA helicase.
Combinatorial Chemistry & High Throughput Screening
Title:Establishment of a Primary Screening Assay for the DHX9 Helicase
Volume: 18 Issue: 9
Author(s): Regina Cencic, Patrick Senechal and Jerry Pelletier
Affiliation:
Keywords: ATPase assay, ATA, aurintricarboxylic acid, DHX9, HTS, RNA binding, RNA 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.
Export Options
About this article
Cite this article as:
Cencic Regina, Senechal Patrick and Pelletier Jerry, Establishment of a Primary Screening Assay for the DHX9 Helicase, Combinatorial Chemistry & High Throughput Screening 2015; 18 (9) . https://dx.doi.org/10.2174/1386207318666151019093433
DOI https://dx.doi.org/10.2174/1386207318666151019093433 |
Print ISSN 1386-2073 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5402 |
Call for Papers in Thematic Issues
Artificial Intelligence Methods for Biomedical, Biochemical and Bioinformatics Problems
Recently, a large number of technologies based on artificial intelligence have been developed and applied to solve a diverse range of problems in the areas of biomedical, biochemical and bioinformatics problems. By utilizing powerful computing resources and massive amounts of data, methods based on artificial intelligence can significantly improve the ...read more
Eco-friendly Agents for Biological Control of Pathogenic Diseases
The discovery of an alternative biological approach to disease management includes work on medicinal products derived from natural sources as a starting point for the development of eco-friendly agents for these diseases and the injuries they cause, as well as reducing human contact with hazardous chemicals and their residues. We ...read more
Emerging trends in diseases mechanisms, noble drug targets and therapeutic strategies: focus on immunological and inflammatory disorders
Recently infectious and inflammatory diseases have been a key concern worldwide due to tremendous morbidity and mortality world Wide. Recent, nCOVID-9 pandemic is a good example for the emerging infectious disease outbreak. The world is facing many emerging and re-emerging diseases out breaks at present however, there is huge lack ...read more
Exploring Spectral Graph Theory in Combinatorial Chemistry
Scope of the Thematic Issue: Combinatorial chemistry involves the synthesis and analysis of a large number of diverse compounds simultaneously. Traditional methods rely on brute force experimentation, which can be time-consuming and resource-intensive. Spectral Graph Theory, a branch of mathematics dealing with the properties of graphs in relation to the ...read more
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
Related Articles
-
Systemic Therapeutic Gene Delivery for Cancer: Crafting Paris Arrow
Current Gene Therapy “Smart” Nanocarriers: A New Paradigm for Tumor Targeting Drug Delivery Systems
Drug Delivery Letters Polypurine Reverse Hoogsteen Hairpins as a Gene Silencing Tool for Cancer
Current Medicinal Chemistry AIDS-Related Kaposis Sarcoma: State of the Art and Therapeutic Strategies
Current HIV Research Response to HAART in Treatment-Naive HIV-Infected Patients with a Prior Diagnosis of Tuberculosis or other Opportunistic Infections
Current HIV Research Recent Developments in the Regulation of Monoamine Oxidase Form and Function: Is the Current Model Restricting Our Understanding of the Breadth of Contribution of Monoamine Oxidase to Brain [dys]Function?
Current Topics in Medicinal Chemistry Double-Faced Role of Human Mesenchymal Stem Cells and their Role/Challenges in Cancer Therapy
Current Stem Cell Research & Therapy Platinum-Intercalator Conjugates: From DNA-Targeted Cisplatin Derivatives to Adenine Binding Complexes as Potential Modulators of Gene Regulation
Current Topics in Medicinal Chemistry Predictive Factors of Febrile Neutropenia Induced by Anticancer Chemotherapy in the South of Tunisia
Reviews on Recent Clinical Trials Doxsaliform: A Novel N-Mannich Base Prodrug of a Doxorubicin Formaldehyde Conjugate
Letters in Drug Design & Discovery Pharmacogenetics of Oxazaphosphorines and its Clinical Implications
Current Pharmacogenomics Prevention and Treatment of Bone Metastases
Current Pharmaceutical Design Intracellular Logistics of BST-2/Tetherin
Current HIV Research Manipulation of the Immune System for Cancer Defeat: A Focus on the T Cell Inhibitory Checkpoint Molecules
Current Medicinal Chemistry Targeting Microparticle Biogenesis: A Novel Approach to the Circumvention of Cancer Multidrug Resistance
Current Cancer Drug Targets High-Throughput Functional Genomic Methods to Analyze the Effects of Dietary Lipids
Current Pharmaceutical Biotechnology Intracellular Delivery of Potential Therapeutic Genes: Prospects in Cancer Gene Therapy
Current Gene Therapy The Posttranslational Phase of Gene Expression: New Possibilities in Molecular Diagnosis
Current Molecular Medicine Bortezomib: A New Pro-Apoptotic Agent in Cancer Treatment
Current Cancer Drug Targets Cancer Stem Cells – Are Surface Markers Alone Sufficient?
Current Stem Cell Research & Therapy