Interaction between ATM and PARP-1 in response to DNA damage and sensitization of ATM deficient cells through PARP inhibition Aguilar-Quesada, Rocío Muñoz Gámez, José Antonio Martín-Oliva, David Peralta, Andreina Valenzuela, María Teresa Martínez-Romero, Rubén Quiles-Pérez, Rosa Menisier de Murcia, Josiane Murcia, Gilbert de Ruiz De Almodóvar Rivera, José Mariano Oliver Pozo, Francisco Javier Parp-1 Oncogene Serum Albumin Protein Kinase Ataxia Antibodies 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 γ-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 γ-H2AX foci formation in response to γ-irradiation, PARP inhibition on itself is able to activate ATM-kinase. PARP inhibition induced γ 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. 2014-07-23T07:45:51Z 2014-07-23T07:45:51Z 2007 info:eu-repo/semantics/article Aguilar-Quesada, R.; et al. Interaction between ATM and PARP-1 in response to DNA damage and sensitization of ATM deficient cells through PARP inhibition. BMC Molecular Biology, 8: 29 (2007). [http://hdl.handle.net/10481/32744] 1471-2199 http://hdl.handle.net/10481/32744 10.1186/1471-2199-8-29 eng http://creativecommons.org/licenses/by-nc-nd/3.0/ info:eu-repo/semantics/openAccess Creative Commons Attribution-NonCommercial-NoDerivs 3.0 License Biomed Central