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 journalArticlepeer-review


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
Issue number4
Publication statusPublished - Dec 1 2002

ASJC Scopus subject areas

  • Genetics(clinical)
  • Genetics


Dive into the research topics of 'A myogenic differentiation checkpoint activated by genotoxic stress'. Together they form a unique fingerprint.

Cite this