KAT5 tyrosine phosphorylation couples chromatin sensing to ATM signalling

Abderrahmane Kaidi and Stephen P. Jackson ()
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Abderrahmane Kaidi: University of Cambridge
Stephen P. Jackson: University of Cambridge

Nature, 2013, vol. 498, issue 7452, 70-74

Abstract: Abstract The detection of DNA lesions within chromatin represents a critical step in cellular responses to DNA damage. However, the regulatory mechanisms that couple chromatin sensing to DNA-damage signalling in mammalian cells are not well understood. Here we show that tyrosine phosphorylation of the protein acetyltransferase KAT5 (also known as TIP60) increases after DNA damage in a manner that promotes KAT5 binding to the histone mark H3K9me3. This triggers KAT5-mediated acetylation of the ATM kinase, promoting DNA-damage-checkpoint activation and cell survival. We also establish that chromatin alterations can themselves enhance KAT5 tyrosine phosphorylation and ATM-dependent signalling, and identify the proto-oncogene c-Abl as a mediator of this modification. These findings define KAT5 tyrosine phosphorylation as a key event in the sensing of genomic and chromatin perturbations, and highlight a key role for c-Abl in such processes.

Date: 2013
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DOI: 10.1038/nature12201

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