title: Recognition of intermolecular G-quadruplexes by full length nucleophosmin. Effect of a leukaemia-associated mutation.
abstract: Nucleophosmin (NPM) is a nucleolar protein involved in ribosome biogenesis. NPM1 gene is frequently mutated in acute myeloid leukaemia (AML), correlating with aberrant cytoplasmic localization of the protein. NPM attachment to the nucleolus in physiological conditions probably depends on binding to nucleic acids, and this recognition could be altered in AML. NPM associates to guanine-rich DNA sequences, able to fold as "G-quadruplexes". We have analyzed the interaction of pentameric, full length NPM with G-rich oligonucleotides, finding that the protein binds preferentially high-order G-quadruplexes. AML-associated mutation significantly hampers DNA binding, pointing to a possible mechanism contributing to pathological mislocalization of NPM.
authors.affiliation: Biophysics Unit (CSIC/UPV-EHU), Department of Biochemistry and Molecular Biology, University of Basque Country (UPV-EHU), POB 644, 48080 Bilbao, Spain. sonia.banuelos@ehu.es
authors.forename: Sonia
authors.initials: S
authors.lastname: Bañuelos
authors.forename: Benoît
authors.initials: B
authors.lastname: Lectez
authors.forename: Stefka G
authors.initials: SG
authors.lastname: Taneva
authors.forename: Georgina
authors.initials: G
authors.lastname: Ormaza
authors.forename: Marián
authors.initials: M
authors.lastname: Alonso-Mariño
authors.forename: Xabier
authors.initials: X
authors.lastname: Calle
authors.forename: María A
authors.initials: MA
authors.lastname: Urbaneja
mesh_terms: D002850:Chromatography, Gel; D024202:Electrophoretic Mobility Shift Assay; D054856:G-Quadruplexes; D016259:Genes, myc; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000235:genetics*; D009154:Mutation; D009687:Nuclear Proteins / Q000737:chemistry* / Q000235:genetics; D000090243:Nucleophosmin; D011485:Protein Binding; D013816:Thermodynamics
chemical_list: C000716967:NPM1 protein, human; D009687:Nuclear Proteins; D000090243:Nucleophosmin