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

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dc.creator Aguilar-Quesada, Rocío
dc.creator Muñoz-Gámez, José A.
dc.creator Martín-Oliva, David
dc.creator Peralta, Andreína
dc.creator Valenzuela, María Teresa
dc.creator Matínez-Romero, Rubén
dc.creator Quiles-Pérez, Rosa
dc.creator Menissier-de Murcia, Josiane
dc.creator Murcia, Gilbert de
dc.creator Ruiz de Almodóvar, José Mariano
dc.creator Oliver, Francisco Javier
dc.date 2008-04-02T09:45:49Z
dc.date 2008-04-02T09:45:49Z
dc.date 2007-04-25
dc.date.accessioned 2017-01-31T01:01:25Z
dc.date.available 2017-01-31T01:01:25Z
dc.identifier BMC Mol Biol. 2007; 8: 29
dc.identifier 1471-2199
dc.identifier http://hdl.handle.net/10261/3414
dc.identifier 10.1186/1471-2199-8-29
dc.identifier.uri http://dspace.mediu.edu.my:8181/xmlui/handle/10261/3414
dc.description This article is available from: http://www.biomedcentral.com/1471-2199/8/29
dc.description 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 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.
dc.description 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.
dc.description Peer reviewed
dc.format 465839 bytes
dc.format application/pdf
dc.language eng
dc.publisher BioMed Central
dc.relation Publisher’s version
dc.rights openAccess
dc.title Interaction between ATM and PARP-1 in response to DNA damage and sensitization of ATM deficient cells through PARP inhibition
dc.type Artículo


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