We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
DNA damage activates ATM through intermolecular autophosphorylation and dimer dissociation.
- Authors
Bakkenist, Christopher J; Kastan, Michael B
- Abstract
The ATM protein kinase, mutations of which are associated with the human disease ataxia-telangiectasia, mediates responses to ionizing radiation in mammalian cells. Here we show that ATM is held inactive in unirradiated cells as a dimer or higher-order multimer, with the kinase domain bound to a region surrounding serine 1981 that is contained within the previously described 'FAT' domain. Cellular irradiation induces rapid intermolecular autophosphorylation of serine 1981 that causes dimer dissociation and initiates cellular ATM kinase activity. Most ATM molecules in the cell are rapidly phosphorylated on this site after doses of radiation as low as 0.5 Gy, and binding of a phosphospecific antibody is detectable after the introduction of only a few DNA double-strand breaks in the cell. Activation of the ATM kinase seems to be an initiating event in cellular responses to irradiation, and our data indicate that ATM activation is not dependent on direct binding to DNA strand breaks, but may result from changes in the structure of chromatin.
- Publication
Nature, 2003, Vol 421, Issue 6922, p499
- ISSN
0028-0836
- Publication type
Journal Article
- DOI
10.1038/nature01368