2. Academic Validation
  3. ADP-ribose-derived nuclear ATP synthesis by NUDIX5 is required for chromatin remodeling

ADP-ribose-derived nuclear ATP synthesis by NUDIX5 is required for chromatin remodeling

  • Science. 2016 Jun 3;352(6290):1221-5. doi: 10.1126/science.aad9335.
Roni H G Wright 1,  Antonios Lioutas 1,  Francois Le Dily 1,  Daniel Soronellas 1,  Andy Pohl 1,  Jaume Bonet 2,  A S Nacht 1,  Sara Samino 3,  Jofre Font-Mateu 1,  Guillermo P Vicent 1,  Michael Wierer 1,  Miriam A Trabado 4,  Constanze Schelhorn 5,  Carlo Carolis 4,  Maria J Macias 6,  Oscar Yanes 3,  Baldo Oliva 2,  Miguel Beato 7
Affiliations

Affiliations

  • 1 Centre de Regulació Genòmica (CRG), Barcelona Institute for Science and Technology, Barcelona E-09003, Spain. Universitat Pompeu Fabra, Barcelona E-08003, Spain.
  • 2 Universitat Pompeu Fabra, Barcelona E-08003, Spain. Structural Bioinformatics Laboratory, Universitat Pompeu Fabra, Barcelona E-08003, Spain.
  • 3 Metabolomics Platform, Spanish Biomedical Research Centre in Diabetes and Associated Metabolic Disorders (CIBERDEM), 28029 Madrid, Spain. Center for Omic Sciences and Department of Electronic Engineering, Rovira i Virgili University, 43007 Tarragona, Spain.
  • 4 Biomolecular Screening and Protein Technologies Unit, Centre de Regulació Genòmica, Barcelona E-08003, Spain.
  • 5 Institute for Research in Biomedicine (IRB Barcelona), Barcelona Institute of Science and Technology, Barcelona 08028, Spain.
  • 6 Institute for Research in Biomedicine (IRB Barcelona), Barcelona Institute of Science and Technology, Barcelona 08028, Spain. Catalan Institution for Research and Advanced Studies (ICREA), Barcelona, Spain.
  • 7 Centre de Regulació Genòmica (CRG), Barcelona Institute for Science and Technology, Barcelona E-09003, Spain. Universitat Pompeu Fabra, Barcelona E-08003, Spain. miguel.beato@crg.eu.
PMID: 27257257 DOI: 10.1126/science.aad9335
Abstract

Key nuclear processes in eukaryotes, including DNA replication, repair, and gene regulation, require extensive chromatin remodeling catalyzed by energy-consuming Enzymes. It remains unclear how the ATP demands of such processes are met in response to rapid stimuli. We analyzed this question in the context of the massive gene regulation changes induced by progestins in breast Cancer cells and found that ATP is generated in the cell nucleus via the hydrolysis of poly(ADP-ribose) to ADP-ribose. In the presence of pyrophosphate, ADP-ribose is used by the pyrophosphatase NUDIX5 to generate nuclear ATP. The nuclear source of ATP is essential for hormone-induced chromatin remodeling, transcriptional regulation, and cell proliferation.

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