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Por favor, use este identificador para citar o enlazar a este item: http://hdl.handle.net/10261/3414
Título

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

AutorAguilar-Quesada, Rocío; Muñoz-Gámez, José A.; Martín-Oliva, David; Peralta, Andreína; Valenzuela, María Teresa; Matínez-Romero, Rubén; Quiles-Pérez, Rosa; Menissier-de Murcia, Josiane; Murcia, Gilbert de; Ruiz de Almodóvar, José Mariano; Oliver, Francisco Javier
Fecha de publicación25-abr-2007
EditorBioMed Central
CitaciónBMC Mol Biol. 2007; 8: 29
ResumenATM 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 ATMkinase 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 ATMdependent 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.
DescripciónThis article is available from: http://www.biomedcentral.com/1471-2199/8/29
URIhttp://hdl.handle.net/10261/3414
DOI10.1186/1471-2199-8-29
ISSN1471-2199
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