To maintain genomic integrity, eukaryotic cells have cell-cycle checkpoints, signal transduction pathways that detect DNA damage and halt the cell cycle until the damage is repaired. Now Anastasis Stephanou and colleagues report that the signalling molecule STAT-1 (signal transducer and activator of transcription 1) facilitates the ATM-mediated checkpoints induced after DNA damage caused by ionizing radiation (see ). STAT-1, a possible tumour suppressor, plays a role in interferon-mediated growth arrest and apoptosis. To discover how STAT-1 inhibits cell growth, the authors examine its role in DNA-damage response pathways in mouse and human cells. They show that STAT-1-deficient cells have defects in the intra-S and G2-M checkpoint responses to DNA damage. These defects include reduced phosphorylation of the checkpoint kinase Chk2 and of some downstream targets of the ATM kinase. The expression of MDC1 and 53BP1, two proteins required for ATM-mediated checkpoints, is also reduced in STAT-1-deficient cells; enforced MDC1 expression restores ATM-mediated phosphorylation of downstream substrates. The authors conclude that STAT-1 plays a crucial role in modulating cell-cycle-checkpoint responses after DNA damage.
