title: MYC impairs resolution of site-specific DNA double-strand breaks repair.
abstract: Although it is established that when overexpressed, the MYC family proteins can cause DNA double-stand breaks (DSBs) and genome instability, the mechanisms involved remain unclear. MYC induced genetic instability may result from increased DNA damage and/or reduced DNA repair. Here we show that when overexpressed, MYC proteins induce a sustained DNA damage response (DDR) and reduce the wave of DSBs repair. We used a cell-based DSBs system whereby, upon induction of an inducible restriction enzyme AsiSI, hundreds of site-specific DSBs are generated across the genome to investigate the role of MYC proteins on DSB. We found that high levels of MYC do not block accumulation of γH2AX at AsiSI sites, but delay its clearance, indicating an inefficient repair, while the initial recognition of DNA damage is largely unaffected. Repair of both homologous and nonhomologous repair-prone segments, characterized by high or low levels of recruited RAD51, respectively, was delayed. Collectively, these data indicate that high levels of MYC proteins delay the resolution of DNA lesions engineered to occur in cell cultures.
authors.affiliation: Department of Biology, University of Naples 'Federico II', Naples, Italy.
authors.forename: Susanna
authors.initials: S
authors.lastname: Ambrosio
authors.affiliation: Department of Molecular Medicine and Medical Biotechnologies, University of Naples 'Federico II', Naples, Italy.
authors.forename: Stefano
authors.initials: S
authors.lastname: Amente
authors.affiliation: Department of Biology, University of Naples 'Federico II', Naples, Italy.
authors.forename: Giuliana
authors.initials: G
authors.lastname: Napolitano
authors.affiliation: Department of Molecular Medicine and Medical Biotechnologies, University of Naples 'Federico II', Naples, Italy.
authors.forename: Giacomo
authors.initials: G
authors.lastname: Di Palo
authors.affiliation: Department of Molecular Medicine and Medical Biotechnologies, University of Naples 'Federico II', Naples, Italy. Electronic address: lania@unina.it.
authors.forename: Luigi
authors.initials: L
authors.lastname: Lania
authors.affiliation: Department of Biology, University of Naples 'Federico II', Naples, Italy. Electronic address: majello@unina.it.
authors.forename: Barbara
authors.initials: B
authors.lastname: Majello
mesh_terms: D001665:Binding Sites / Q000235:genetics; D015153:Blotting, Western; D002453:Cell Cycle / Q000235:genetics; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism; D045744:Cell Line, Tumor; D004247:DNA / Q000235:genetics / Q000378:metabolism*; D053903:DNA Breaks, Double-Stranded; D004260:DNA Repair; D004262:DNA Restriction Enzymes / Q000378:metabolism; D006657:Histones / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008856:Microscopy, Fluorescence; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics / Q000378:metabolism*; D051135:Rad51 Recombinase / Q000235:genetics / Q000378:metabolism
chemical_list: D018797:Cell Cycle Proteins; C468783:H2AX protein, human; D006657:Histones; C112156:NBN protein, human; D009687:Nuclear Proteins; D016271:Proto-Oncogene Proteins c-myc; D004247:DNA; D051135:Rad51 Recombinase; D004262:DNA Restriction Enzymes
keywords: AsiSI restriction enzyme; DSB repair; MYC; MYCN; Site-specific DSBs