Editors' ChoiceCell Biology

Stress, DNA Damage, and ATM

Science Signaling  26 Oct 2010:
Vol. 3, Issue 145, pp. ec329
DOI: 10.1126/scisignal.3145ec329

The protein kinase ATM (ataxia-telangiectasia mutated) is a key component of the signaling pathway through which cells are protected from DNA damage. ATM becomes activated within a protein complex at sites of double-stranded breaks in DNA. ATM is also activated in response to increased production of reactive oxygen species (ROS). Such activation was thought to reflect DNA damage caused by ROS, but Guo et al. showed that ATM was in fact directly activated by ROS. A cysteine residue in ATM contributes to the formation of disulfide-linked dimers of activated ATM on exposure to ROS in vitro. Experiments using mutated forms of the enzyme suggested that two distinct mechanisms regulated ATM activity.

Z. Guo, S. Kozlov, M. F. Lavin, M. D. Person, T. T. Paull, ATM activation by oxidative stress. Science 330, 517–521 (2010). [Abstract] [Full Text]