當DNA發(fā)生雙鏈斷裂時,，ATM (ataxia telangiectasia mutated) 激酶便被激發(fā),。“乙酰轉(zhuǎn)移酶” KAT5 向被修飾的組蛋白標記物H3K9me3上的結(jié)合通過使該激酶乙酰化來促進ATM激發(fā),。在這篇文章中,，Abderrahmane Kaidi 和 Stephen Jackson 發(fā)現(xiàn)，在DNA損傷后,，c-Abl激酶磷酸化“酪氨酸44”上的KAT5,，增強其與H3K9me3的相互作用，并允許由ATM介導的信號作用來啟動DNA損傷檢查點,。這些發(fā)現(xiàn)也許可幫助解釋“賴氨酸脫乙?；?rdquo;（它們作為治療藥物正在研發(fā)中）的作用機制，因此也許還能為應(yīng)該怎樣最好地將這類藥物用于癌癥和神經(jīng)退化疾病的治療提供線索,。(生物谷Bioon.com)

生物谷推薦英文摘要：

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.