Overview:

ATM is a master regulator for dsDNA break repair, which belongs to the phosphoinositide 3-kinase (PI(3)K) superfamily. Unlike other lipid kinases, ATM phosphorylates proteins. ATM is present in undamaged cells as an inactive dimer, which is activated likely in response to changes in chromatin structure. Exposure of cells to ionizing radiation triggers ATM kinase activity, leading to cell cycle arrest in the G1, S or G2 phase. Several substrates of the ATM kinase participate in these IR-induced cell-cycle arrests. These include p53, MDM2 and CHK2 in the G1 checkpoint; NBS1, BRCA1, FancD2 and SMC1 in the transient IR-induced S-phase arrest; and BRCA1 and hRAD17 during the G2/M checkpoint. ATM is mutated in the hereditary disease ataxia-telangiectasia.

References:

1. Bakkenist, C. J., et al.: DNA damage activates ATM through intermolecular autophosphorylation and dimer dissociation. Nature. 2003: 421; 499-506.

2. Kitagawa R, et al.: Phosphorylation of SMC1 is a critical downstream event in the ATM-NBS1-BRCA1 pathway. Genes Dev. 2004: 18(12);1423-38.

3. Falck, J. et al.: Conserved modes of recruitment of ATM, ATR and DNA-PKcs to sites of DNA damage. Nature. 2005: 434; 605-611.