title: DNA-PK activity is associated with caspase-dependent myogenic differentiation.
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.
authors: Pharmacology and Therapeutics, School of Medicine, National University of Ireland Galway, Ireland.
authors: Patrick F
authors: PF
authors: Connolly
authors: Pharmacology and Therapeutics, School of Medicine, National University of Ireland Galway, Ireland. howard.fearnhead@nuigalway.ie.
authors: Howard O
authors: HO
authors: Fearnhead
mesh_terms: D000818:Animals; D053148:Caspase 3 / Q000378:metabolism*; D061945:Caspase Inhibitors / Q000494:pharmacology; D002459:Cell Fusion; D002460:Cell Line; D002867:Chromones / Q000494:pharmacology; D004249:DNA Damage; D051747:DNA-Activated Protein Kinase / Q000037:antagonists & inhibitors / Q000502:physiology*; D006657:Histones / Q000378:metabolism; D051379:Mice; D009025:Morpholines / Q000494:pharmacology; D024510:Muscle Development / Q000187:drug effects / Q000235:genetics; D032446:Myoblasts / Q000187:drug effects / Q000201:enzymology; D010766:Phosphorylation / Q000187:drug effects; D047428:Protein Kinase Inhibitors / Q000494:pharmacology
chemical_list: D053148:Caspase 3; D061945:Caspase Inhibitors; D002867:Chromones; D051747:DNA-Activated Protein Kinase; D006657:Histones; D009025:Morpholines; D047428:Protein Kinase Inhibitors; C479235:2-(morpholin-4-yl)benzo(h)chromen-4-one; C499693:8-dibenzothiophen-4-yl-2-morpholin-4-yl-chromen-4-one; C475961:gamma-H2AX protein, mouse
keywords: DNA-PK; DNA-damage; apoptosis; caspase-3; differentiation; muscle; myogenesis