This article is available from: http://www.biomedcentral.com/1471-2199/8/29
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.
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.
Peer reviewed