title: ADP-ribose-derived nuclear ATP synthesis by NUDIX5 is required for chromatin remodeling.
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.
authors.affiliation: Centre de Regulació Genòmica (CRG), Barcelona Institute for Science and Technology, Barcelona E-09003, Spain. Universitat Pompeu Fabra, Barcelona E-08003, Spain.
authors.forename: Roni H G
authors.initials: RH
authors.lastname: Wright
authors.affiliation: Centre de Regulació Genòmica (CRG), Barcelona Institute for Science and Technology, Barcelona E-09003, Spain. Universitat Pompeu Fabra, Barcelona E-08003, Spain.
authors.forename: Antonios
authors.initials: A
authors.lastname: Lioutas
authors.affiliation: Centre de Regulació Genòmica (CRG), Barcelona Institute for Science and Technology, Barcelona E-09003, Spain. Universitat Pompeu Fabra, Barcelona E-08003, Spain.
authors.forename: Francois
authors.initials: F
authors.lastname: Le Dily
authors.affiliation: Centre de Regulació Genòmica (CRG), Barcelona Institute for Science and Technology, Barcelona E-09003, Spain. Universitat Pompeu Fabra, Barcelona E-08003, Spain.
authors.forename: Daniel
authors.initials: D
authors.lastname: Soronellas
authors.affiliation: Centre de Regulació Genòmica (CRG), Barcelona Institute for Science and Technology, Barcelona E-09003, Spain. Universitat Pompeu Fabra, Barcelona E-08003, Spain.
authors.forename: Andy
authors.initials: A
authors.lastname: Pohl
authors.affiliation: Universitat Pompeu Fabra, Barcelona E-08003, Spain. Structural Bioinformatics Laboratory, Universitat Pompeu Fabra, Barcelona E-08003, Spain.
authors.forename: Jaume
authors.initials: J
authors.lastname: Bonet
authors.affiliation: Centre de Regulació Genòmica (CRG), Barcelona Institute for Science and Technology, Barcelona E-09003, Spain. Universitat Pompeu Fabra, Barcelona E-08003, Spain.
authors.forename: A S
authors.initials: AS
authors.lastname: Nacht
authors.affiliation: 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.
authors.forename: Sara
authors.initials: S
authors.lastname: Samino
authors.affiliation: Centre de Regulació Genòmica (CRG), Barcelona Institute for Science and Technology, Barcelona E-09003, Spain. Universitat Pompeu Fabra, Barcelona E-08003, Spain.
authors.forename: Jofre
authors.initials: J
authors.lastname: Font-Mateu
authors.affiliation: Centre de Regulació Genòmica (CRG), Barcelona Institute for Science and Technology, Barcelona E-09003, Spain. Universitat Pompeu Fabra, Barcelona E-08003, Spain.
authors.forename: Guillermo P
authors.initials: GP
authors.lastname: Vicent
authors.affiliation: Centre de Regulació Genòmica (CRG), Barcelona Institute for Science and Technology, Barcelona E-09003, Spain. Universitat Pompeu Fabra, Barcelona E-08003, Spain.
authors.forename: Michael
authors.initials: M
authors.lastname: Wierer
authors.affiliation: Biomolecular Screening and Protein Technologies Unit, Centre de Regulació Genòmica, Barcelona E-08003, Spain.
authors.forename: Miriam A
authors.initials: MA
authors.lastname: Trabado
authors.affiliation: Institute for Research in Biomedicine (IRB Barcelona), Barcelona Institute of Science and Technology, Barcelona 08028, Spain.
authors.forename: Constanze
authors.initials: C
authors.lastname: Schelhorn
authors.affiliation: Biomolecular Screening and Protein Technologies Unit, Centre de Regulació Genòmica, Barcelona E-08003, Spain.
authors.forename: Carlo
authors.initials: C
authors.lastname: Carolis
authors.affiliation: 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.
authors.forename: Maria J
authors.initials: MJ
authors.lastname: Macias
authors.affiliation: 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.
authors.forename: Oscar
authors.initials: O
authors.lastname: Yanes
authors.affiliation: Universitat Pompeu Fabra, Barcelona E-08003, Spain. Structural Bioinformatics Laboratory, Universitat Pompeu Fabra, Barcelona E-08003, Spain.
authors.forename: Baldo
authors.initials: B
authors.lastname: Oliva
authors.affiliation: 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.
authors.forename: Miguel
authors.initials: M
authors.lastname: Beato
mesh_terms: D000246:Adenosine Diphosphate Ribose / Q000378:metabolism*; D000255:Adenosine Triphosphate / Q000096:biosynthesis*; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism; D002467:Cell Nucleus / Q000187:drug effects / Q000378:metabolism*; D049109:Cell Proliferation; D042002:Chromatin Assembly and Disassembly; D018360:Crystallography, X-Ray; D011756:Diphosphates / Q000378:metabolism; D004734:Energy Metabolism; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D006868:Hydrolysis; D061986:MCF-7 Cells; D000071137:Poly (ADP-Ribose) Polymerase-1; D011064:Poly Adenosine Diphosphate Ribose / Q000378:metabolism; D011065:Poly(ADP-ribose) Polymerases / Q000235:genetics / Q000378:metabolism; D011372:Progestins / Q000378:metabolism* / Q000494:pharmacology; D055503:Protein Multimerization; D011755:Pyrophosphatases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*
chemical_list: D011756:Diphosphates; D011372:Progestins; D000246:Adenosine Diphosphate Ribose; D011064:Poly Adenosine Diphosphate Ribose; C107241:diphosphoric acid; D000255:Adenosine Triphosphate; C499320:PARP1 protein, human; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases; C403715:NUDT5 protein, human; D011755:Pyrophosphatases