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


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.

SUBMITTER: Simonatto M 

PROVIDER: S-EPMC3322469 | biostudies-literature | 2011 Jul

REPOSITORIES: biostudies-literature

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

Simonatto Marta M   Giordani Lorenzo L   Marullo Fabrizia F   Minetti Giulia Claudia GC   Puri Pier Lorenzo PL   Latella Lucia L  

Cell cycle (Georgetown, Tex.) 20110715 14


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  ...[more]

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