DNA Damage-Transcription Links

Science's STKE  28 Feb 2006:
Vol. 2006, Issue 324, pp. tw79
DOI: 10.1126/stke.3242006tw79

Damage to DNA in cells (like that produced by some anticancer drugs) is sensed by the cell and causes cellular responses that determine whether a cell lives or dies. Wu et al. (see the Perspective by Bartek and Lukas) provide a new link by which this signal can be conveyed from the nucleus to the cytoplasm. The protein kinase ataxia telangiectasia mutated (ATM) is activated in response to DNA damage and directly phosphorylates NEMO, one of the proteins in the IκB kinase (IKK) complex that regulates the activity of the transcription factor NF-κB. NF-κB in turn mediates signals that promote cell survival. After DNA damage, ATM was exported from the nucleus and then interacted in the cytoplasm with another protein in the IKK complex, ELKS. Activated IKK then caused activation of NF-κB-dependent transcription.

Z.-H. Wu, Y. Shi, R. S. Tibbetts, S. Miyamoto, Molecular linkage between the kinase ATM and NF-κB signaling in response to genotoxic stimuli. Science 311, 1141-1146 (2006). [Abstract] [Full Text]

J. Bartek, J. Lukas, The stress of finding NEMO. Science 311, 1110-1111 (2006). [Summary] [Full Text]