被撤回的出版物: KAT5 tyrosine phosphorylation couples chromatin sensing to ATM signalling (Retracted article. See vol. 568, pg. 576, 2019)

[摘要] 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.

[效力级别]  Retracted Publication

[关键词] DNA-DAMAGE RESPONSE;HISTONE H3 METHYLATION;DOUBLE-STRAND BREAKS;C-ABL;ACTIVATES ATM;KINASE;PROTEIN;ACETYLATION;AUTOPHOSPHORYLATION;INHIBITION