Screening strategy for the identification of ATR inhibitors.
Effect of ATRi and DDRi on the G2/M checkpoint.
ATM-, ATR- and DNA-PKcs-dependent phosphorylation in vivo.
ATRi and DDRi promote the breakage of stalled replication forks.
Inhibition of ATR generates replicative stress.
Synthetic lethality of ATR inhibition with cyclin E overexpression and/or p53 loss.
Genomic Instability Group, Spanish National Cancer Research Centre, Madrid, Spain.
- Luis I Toledo,
- Matilde Murga,
- Rafal Zur,
- Rebeca Soria &
- Oscar Fernandez-Capetillo
Experimental Therapeutics Programme, Spanish National Cancer Research Centre, Madrid, Spain.
- Antonio Rodriguez,
- Sonia Martinez,
- Julen Oyarzabal,
- Joaquin Pastor &
- James R Bischoff
Present address: Center for Applied Medical Research, University of Navarra, Pamplona, Spain.
- Julen Oyarzabal
O.F.-C. designed the study and experiments and wrote the paper. L.I.T. conducted most of the experiments presented. M.M. helped in the work with oncogenes and CDC25A. R.Z. and R.S. provided technical help. J.O., A.R., S.M., J.P. and J.R.B. provided the chemicals and helped in the development of the small molecule screening.
Competing financial interests
The authors declare no competing financial interests.
Luis I Toledo
James R Bischoff