DNA‐PK activity is associated with caspase‐dependent myogenic differentiation

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• 作者：Patrick F. Connolly ; Howard O. Fearnhead
• 刊名：FEBS Journal
• 出版年：2016
• 出版时间：October 2016
• 年：2016
• 卷：283
• 期：19
• 页码：3626-3636
• 全文大小：999.4KB
• ISSN：1742-4658

文摘

Differentiation of myoblasts into myotubes is essential for skeletal muscle development and regeneration. Caspase-3 and caspase-9 are required for efficient myoblast differentiation. The caspase-activated endonuclease activity, CAD, and the DNA-damage repair protein XRCC1 have also been shown to be required to complete differentiation. DNA-damage associated with differentiation is accompanied by phosphorylation of Histone 2AX, an event normally catalysed by kinases ATR, ATM or DNA-PK. However, the kinase responsible for phosphorylation during differentiation is not known. Here we show that inhibition of DNA-PK, but not of ATR or ATM, blocked histone phosphorylation during differentiation. We also show that DNA-PK inhibition and siRNA-mediated DNA-PK knockdown blocked cell fusion. These data implicate a new role for DNA-PK in myogenic differentiation.