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Bioessays. 2003 Jul;25(7):627-30.

Checkpoint signaling: epigenetic events sound the DNA strand-breaks alarm to the ATM protein kinase.

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Program in Signal Transduction Research, The Burnham Institute, 10901 North Torrey Pines Road, La Jolla, CA 92130, USA.


The ATM protein kinase is centrally involved in the cellular response to ionizing radiation (IR) and other DNA double-strand-break-inducing insults. Although it has been well established that IR exposure activates the ATM kinase domain, the actual mechanism by which ATM responds to damaged DNA has remained enigmatic. Now, a landmark paper provides strong evidence that DNA-strand breaks trigger widespread activation of ATM through changes in chromatin structure (1). This review discusses a checkpoint activation model in which chromatin perturbations lead to the conversion of inactive ATM domains to phosphorylated, active ATM monomers. The new findings underscore the critical importance of epigenetic events in genome function and surveillance in mammalian cells.

[Indexed for MEDLINE]

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