RT Journal Article
T1 Interaction between ATM and PARP-1 in response to DNA damage and sensitization of ATM deficient cells through PARP inhibition
A1 Aguilar-Quesada, Rocío
A1 Muñoz-Gámez, José Antonio
A1 Martín-Oliva, David
A1 Peralta, Andreína
A1 Valenzuela, Maria Teresa
A1 Matínez-Romero, Rubén
A1 Quiles-Pérez, Rosa
A1 Menissier-de Murcia, Josiane
A1 de Murcia, Gilbert
A1 Ruiz de Almodóvar, Mariano
A1 Oliver, F Javier
K1 DNA-Binding Proteins
K1 Tumor Suppressor Proteins
K1 Adenosine Diphosphate
K1 Poly(ADP-ribose) Polymerases
K1 poly(ADP-ribose)polymerase-1, mouse
K1 Protein-Serine-Threonine Kinases
K1 ataxia telangiectasia mutated protein
K1 Cell Cycle Proteins
K1 Proteínas de Unión al ADN
K1 Proteínas Supresoras de Tumor
K1 Adenosina Difosfato
K1 Poli(ADP-Ribosa) Polimerasas
K1 Poli(ADP-Ribosa) Polimerasas-1
K1 Proteínas Serina-Treonina Quinasas
K1 Ataxia Telangiectasia
K1 Proteínas de Ciclo Celular
K1 Animales
K1 Humanos
AB 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 gamma-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 gamma-H2AX foci formation in response to gamma-irradiation, PARP inhibition on itself is able to activate ATM-kinase. PARP inhibition induced gamma 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.
PB BioMed Central
YR 2007
FD 2007-04-25
LK http://hdl.handle.net/10668/706
UL http://hdl.handle.net/10668/706
LA en
NO Aguilar-Quesada R, Muñoz-Gámez JA, Martín-Oliva D, Peralta A, Valenzuela MT, Matínez-Romero R, et al. Interaction between ATM and PARP-1 in response to DNA damage and sensitization of ATM deficient cells through PARP inhibition. BMC Mol. Biol.2007; 8:29
NO Journal Article; Research Support, Non-U.S. Gov't;
DS RISalud
RD Apr 7, 2025