Research ArticleDNA Repair

Transient ATM Kinase Inhibition Disrupts DNA Damage–Induced Sister Chromatid Exchange

Science Signaling  01 Jun 2010:
Vol. 3, Issue 124, pp. ra44
DOI: 10.1126/scisignal.2000758

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Time and Tools for Repair

ATM is a kinase activated in response to DNA damage, such as that caused by exposure of cells to ionizing radiation. ATM triggers cell cycle checkpoints that allow cells time to repair the damage before proceeding to replicate their DNA. With reversible inhibitors, White et al. show that ATM and DNA-PK, another kinase induced by DNA damage, initiated distinct mechanisms of DNA repair in cells exposed to ionizing radiation. Despite activation of the cell cycle checkpoint, cells in which either of these two kinases was inhibited for as little as 1 hour 15 min after exposure to ionizing radiation exhibited reduced survival and accumulated persistent chromosomal damage. Furthermore, the authors show that ATM-deficient cells adapt and can initiate repair by sister chromatid exchange through an ATM-independent mechanism.