当DNA发生双链断裂时，ATM (ataxia telangiectasia mutated) 激酶便被激发。“乙酰转移酶” KAT5 向被修饰的组蛋白标记物H3K9me3上的结合通过使该激酶乙酰化来促进ATM激发。在这篇文章中，Abderrahmane Kaidi 和 Stephen Jackson 发现，在DNA损伤后，c-Abl激酶磷酸化“酪氨酸44”上的KAT5，增强其与H3K9me3的相互作用，并允许由ATM介导的信号作用来启动DNA损伤检查点。这些发现也许可帮助解释“赖氨酸脱乙酰基酶”（它们作为治疗药物正在研发中）的作用机制，因此也许还能为应该怎样最好地将这类药物用于癌症和神经退化疾病的治疗提供线索。(生物谷Bioon.com)
生物谷推荐英文摘要：
Nature doi:10.1038/nature12201
KAT5 tyrosine phosphorylation couples chromatin sensing to ATM signalling
Abderrahmane Kaidi & Stephen P. Jackson
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.
