Editors' ChoiceCheckpoints

Complex Response to DNA Damage

Science's STKE  06 Apr 2004:
Vol. 2004, Issue 227, pp. tw128
DOI: 10.1126/stke.2272004tw128

Cells avoid the disastrous effects of DNA damage by activating a checkpoint mechanism to prevent proliferation of cells that contain damaged DNA. The protein kinase ATM is an important component of this signaling mechanism, but precisely how its activity is regulated has not been clear. The protein Nbs1, which is mutated in the human disorder Nijmegen breakage syndrome, forms MRN complexes with two other proteins that participate in DNA repair, Mre11 and Rad50 (Mre11-Rad50-Nbs1, hence, MRN). Nbs is also a substrate for ATM. But now, Lee and Paull suggest that the interaction between Nbs1 and ATM is more complicated. MRN complexes directly activate enzymatic activity of ATM, possibly by causing a conformational change in ATM that alters the affinity of the kinase toward its substrates.

J.-H. Lee, T. T. Paull, Direct activation of the ATM protein kinase by the Mre11/Rad50/Nbs1 complex. Science 304, 93-96 (2004). [Abstract] [Full Text]