A myogenic differentiation checkpoint activated by genotoxic stress

Pier Lorenzo Puri, Kunjan Bhakta, Lauren D. Wood, Antonio Costanzo, Jiangyu Zhu, Jean Y J Wang

Research output: Contribution to journalArticle

80 Citations (Scopus)

Abstract

Cell-cycle checkpoints help to protect the genomes of proliferating cells under genotoxic stress. In multicellular organisms, cell proliferation is often directed toward differentiation during development and throughout adult homeostasis. To prevent the formation of differentiated cells with genetic instability, we hypothesized that genotoxic stress may trigger a differentiation checkpoint. Here we show that exposure to genotoxic agents causes a reversible inhibition of myogenic differentiation. Muscle-specific gene expression is suppressed by DNA-damaging agents if applied prior to differentiation induction but not after the differentiation program is established. The myogenic determination factor, MyoD (encoded by Myod1), is a target of the differentiation checkpoint in myoblasts. The inhibition of MyoD by DNA damage requires a functional c-Abl tyrosine kinase (encoded by Abl1), but occurs in cells deficient for p53 (transformation-related protein 53, encoded by Trp53) or c-Jun (encoded by the oncogene Jun). These results support the idea that genotoxic stress can regulate differentiation, and identify a new biological function for DNA damage - activated signaling network.

Original languageEnglish
Pages (from-to)585-593
Number of pages9
JournalNature Genetics
Volume32
Issue number4
DOIs
Publication statusPublished - Dec 1 2002

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DNA Damage
jun Genes
Myoblasts
Cell Cycle Checkpoints
Protein-Tyrosine Kinases
Homeostasis
Cell Proliferation
Genome
Gene Expression
Muscles
DNA
Proteins

ASJC Scopus subject areas

  • Genetics(clinical)
  • Genetics

Cite this

Puri, P. L., Bhakta, K., Wood, L. D., Costanzo, A., Zhu, J., & Wang, J. Y. J. (2002). A myogenic differentiation checkpoint activated by genotoxic stress. Nature Genetics, 32(4), 585-593. https://doi.org/10.1038/ng1023

A myogenic differentiation checkpoint activated by genotoxic stress. / Puri, Pier Lorenzo; Bhakta, Kunjan; Wood, Lauren D.; Costanzo, Antonio; Zhu, Jiangyu; Wang, Jean Y J.

In: Nature Genetics, Vol. 32, No. 4, 01.12.2002, p. 585-593.

Research output: Contribution to journalArticle

Puri, PL, Bhakta, K, Wood, LD, Costanzo, A, Zhu, J & Wang, JYJ 2002, 'A myogenic differentiation checkpoint activated by genotoxic stress', Nature Genetics, vol. 32, no. 4, pp. 585-593. https://doi.org/10.1038/ng1023
Puri PL, Bhakta K, Wood LD, Costanzo A, Zhu J, Wang JYJ. A myogenic differentiation checkpoint activated by genotoxic stress. Nature Genetics. 2002 Dec 1;32(4):585-593. https://doi.org/10.1038/ng1023
Puri, Pier Lorenzo ; Bhakta, Kunjan ; Wood, Lauren D. ; Costanzo, Antonio ; Zhu, Jiangyu ; Wang, Jean Y J. / A myogenic differentiation checkpoint activated by genotoxic stress. In: Nature Genetics. 2002 ; Vol. 32, No. 4. pp. 585-593.
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