KAT5 tyrosine phosphorylation couples chromatin sensing to ATM signalling

Abderrahmane Kaidi, Stephen P Jackson

Research output: Contribution to journalArticle (Academic Journal)peer-review

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.
Original languageEnglish
Pages (from-to)70-74
Number of pages5
JournalNature
Volume498
Issue number7452
Early online date26 May 2013
DOIs
Publication statusPublished - 6 Jun 2013

Keywords

  • Amino Acid Sequence
  • Animals
  • Cell Cycle Checkpoints
  • Cell Cycle Proteins
  • Cell Line
  • Cell Survival
  • Chromatin
  • DNA Damage
  • DNA-Binding Proteins
  • Enzyme Activation
  • HeLa Cells
  • Histone Acetyltransferases
  • Histones
  • Humans
  • Lysine
  • Methylation
  • Molecular Sequence Data
  • Phosphorylation
  • Phosphotyrosine
  • Protein-Serine-Threonine Kinases
  • Proto-Oncogene Proteins c-abl
  • Signal Transduction
  • Tumor Suppressor Proteins

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