Aguilar-Quesada, RocíoMuñoz-Gámez, José AntonioMartín-Oliva, DavidPeralta, AndreínaValenzuela, Maria TeresaMatínez-Romero, RubénQuiles-Pérez, RosaMenissier-de Murcia, Josianede Murcia, GilbertRuiz de Almodóvar, MarianoOliver, F Javier2012-12-112012-12-112007-04-25Aguilar-Quesada R, Muñoz-Gámez JA, Martín-Oliva D, Peralta A, Valenzuela MT, Matínez-Romero R, et al. Interaction between ATM and PARP-1 in response to DNA damage and sensitization of ATM deficient cells through PARP inhibition. BMC Mol. Biol.2007; 8:29http://hdl.handle.net/10668/706Journal Article; Research Support, Non-U.S. Gov't;ATM and PARP-1 are two of the most important players in the cell's response to DNA damage. PARP-1 and ATM recognize and bound to both single and double strand DNA breaks in response to different triggers. Here we report that ATM and PARP-1 form a molecular complex in vivo in undamaged cells and this association increases after gamma-irradiation. ATM is also modified by PARP-1 during DNA damage. We have also evaluated the impact of PARP-1 absence or inhibition on ATM-kinase activity and have found that while PARP-1 deficient cells display a defective ATM-kinase activity and reduced gamma-H2AX foci formation in response to gamma-irradiation, PARP inhibition on itself is able to activate ATM-kinase. PARP inhibition induced gamma H2AX foci accumulation, in an ATM-dependent manner. Inhibition of PARP also induces DNA double strand breaks which were dependent on the presence of ATM. As consequence ATM deficient cells display an increased sensitivity to PARP inhibition. In summary our results show that while PARP-1 is needed in the response of ATM to gamma irradiation, the inhibition of PARP induces DNA double strand breaks (which are resolved in and ATM-dependent pathway) and activates ATM kinase.enDNA-Binding ProteinsTumor Suppressor ProteinsAdenosine DiphosphatePoly(ADP-ribose) Polymerasespoly(ADP-ribose)polymerase-1, mouseProtein-Serine-Threonine Kinasesataxia telangiectasia mutated proteinCell Cycle ProteinsProteínas de Unión al ADNProteínas Supresoras de TumorAdenosina DifosfatoPoli(ADP-Ribosa) PolimerasasPoli(ADP-Ribosa) Polimerasas-1Proteínas Serina-Treonina QuinasasAtaxia TelangiectasiaProteínas de Ciclo CelularAnimalesHumanosMedical Subject Headings::Organisms::Eukaryota::AnimalsMedical Subject Headings::Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins::Cell Cycle ProteinsMedical Subject Headings::Anatomy::Cells::Cells, Cultured::Cell LineMedical Subject Headings::Phenomena and Processes::Genetic Phenomena::Genetic Processes::DNA DamageMedical Subject Headings::Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins::DNA-Binding ProteinsMedical Subject Headings::Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::HumansMedical Subject Headings::Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Rodentia::Muridae::Murinae::MiceMedical Subject Headings::Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Rodentia::Muridae::Murinae::Mice::Mice, Mutant Strains::Mice, KnockoutMedical Subject Headings::Chemicals and Drugs::Enzymes and Coenzymes::Enzymes::Transferases::Glycosyltransferases::Pentosyltransferases::ADP Ribose Transferases::Poly(ADP-ribose) PolymerasesMedical Subject Headings::Phenomena and Processes::Chemical Phenomena::Biochemical Phenomena::Biochemical Processes::Protein BindingMedical Subject Headings::Chemicals and Drugs::Enzymes and Coenzymes::Enzymes::Transferases::Phosphotransferases::Phosphotransferases (Alcohol Group Acceptor)::Protein Kinases::Protein-Serine-Threonine KinasesMedical Subject Headings::Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins::Neoplasm Proteins::Tumor Suppressor ProteinsMedical Subject Headings::Chemicals and Drugs::Heterocyclic Compounds::Heterocyclic Compounds, 2-Ring::Purines::Purine Nucleotides::Adenine Nucleotides::Adenosine Diphosphateresearch article17459151open access10.1186/1471-2199-8-291471-2199