Cells need to be able to respond to DNA damage to restrict its consequences for the organism as a whole. Dornan et al. found a new target for the protein kinase ATM (which, when mutated, causes ataxia telangectasia, a disease that renders patients sensitive to ionizing radiation and an increased risk of cancer). ATM is activated in response to DNA damage and phosphorylates COP1, an E3 ubiquitin ligase that controls ubiquitination and degradation of the key tumor suppressor protein p53. This phosphorylation appears to cause COP1 to turn on itself, mediating its own autoubiquitination and consequent degradation, leading to the accumulation of p53. In tissue cultures, this phosphorylation event appears to be necessary for p53-dependent tumor suppressor activity in response to DNA damaging agents.
D. Dornan, H. Shimizu, A. Mah, T. Dudhela, M. Eby, K. O'Rourke, S. Seshagiri, V. M. Dixit, ATM engages autodegradation of the E3 ubiquitin ligase COP1 after DNA damage. Science 313, 1122-1126 (2006). [Abstract] [Full Text]