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Open Access Highly Accessed Research article

Interaction between ATM and PARP-1 in response to DNA damage and sensitization of ATM deficient cells through PARP inhibition

Rocío Aguilar-Quesada1, José Antonio Muñoz-Gámez12, David Martín-Oliva13, Andreína Peralta1, Ma Teresa Valenzuela2, Rubén Matínez-Romero1, Rosa Quiles-Pérez4, Josiane Menissier-de Murcia5, Gilbert de Murcia5, Mariano Ruiz de Almodóvar2 and F Javier Oliver1*

Author Affiliations

1 Instituto López Neyra de Parasitología y Biomedicina López Neyra, CSIC. Granada, Spain

2 IBIMER, Universidad de Granada, Granada, Spain

3 Dept. Biología Celular, Universidad de Granada, Granada, Spain

4 Hospital Universitario San Cecilio, Granada, Spain

5 Département "Intégrité du Génome" de l'UMR 7175 École Supérieure de Biotechnologie de Strasbourg, Strasbourg, France

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BMC Molecular Biology 2007, 8:29  doi:10.1186/1471-2199-8-29

Published: 25 April 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.