Coordination of cell cycle, DNA repair and muscle gene expression in myoblasts exposed to genotoxic stress

Marta Simonatto, Lorenzo Giordani, Fabrizia Marullo, Giulia Claudia Minetti, Pier Lorenzo Puri, Lucia Latella

Research output: Contribution to journalArticle

Abstract

Upon exposure to genotoxic stress, skeletal muscle progenitors coordinate DNA repair and the activation of the differentiation program, through the DNA damage-activated differentiation checkpoint, which holds the transcription of differentiation genes while the DNA is repaired. A conceptual hurdle intrinsic to this process relates to the coordination of DNA repair and muscle-specific gene transcription within specific cell cycle boundaries (cell cycle checkpoints) activated by different types of genotoxins. Here we show that in proliferating myoblasts, the inhibition of muscle gene transcription occurs by either a G 1- or G 2-specific differentiation checkpoint. In response to genotoxins that induce G 1 arrest, MyoD binds target genes, but is functionally inactivated by a c-Abl dependent phosphorylation. In contrast, DNA damage-activated G 2 checkpoint relies on the inability of MyoD to bind the chromatin at the G 2 phase of the cell cycle. These results indicate an intimate relationship between DNA damage-activated cell cycle checkpoints and the control of tissue-specific gene expression to allow DNA repair in myoblasts prior to the activation of the differentiation program.

Original languageEnglish
Pages (from-to)2355-2363
Number of pages9
JournalCell Cycle
Volume10
Issue number14
DOIs
Publication statusPublished - Jul 15 2011

Keywords

  • Cell cycle
  • DNA damage
  • Muscle differentiation
  • MyoD

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Biology
  • Developmental Biology

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