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Please use this identifier to cite or link to this item: http://hdl.handle.net/10481/32744

Title: Interaction between ATM and PARP-1 in response to DNA damage and sensitization of ATM deficient cells through PARP inhibition
Authors: 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, Mariano
Oliver Pozo, Francisco Javier
Issue Date: 2007
Abstract: 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.
Sponsorship: This work has been supported by grants SAF 2003-01217, RNIHG c03/02, PI050972, SAF2006-01089 and FIS G03/152 to FJO, grants CICYT SAF:2001–3533 and SAF2004-00889 to JMRdA; grant FIS c03/02 to RQP.
Publisher: Biomed Central
Keywords: Parp-1
Oncogene
Serum Albumin
Protein Kinase
Ataxia
Antibodies
URI: http://hdl.handle.net/10481/32744
ISSN: 1471-2199
Rights : Creative Commons Attribution-NonCommercial-NoDerivs 3.0 License
Citation: 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]
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