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FEBS J. 2016 Oct;283(19):3626-3636. doi: 10.1111/febs.13832.

DNA-PK activity is associated with caspase-dependent myogenic differentiation.

Author information

1
Pharmacology and Therapeutics, School of Medicine, National University of Ireland Galway, Ireland.
2
Pharmacology and Therapeutics, School of Medicine, National University of Ireland Galway, Ireland. howard.fearnhead@nuigalway.ie.

Abstract

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.

KEYWORDS:

DNA-PK; DNA-damage; apoptosis; caspase-3; differentiation; muscle; myogenesis

PMID:
27513301
DOI:
10.1111/febs.13832
[Indexed for MEDLINE]
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