Muscle checkpoint

Cell cycle checkpoints ensure that damaged DNA is repaired prior to cell division. In an Advanced Online Publication in Nature Genetics, Pier Puri and colleagues describe the characterization of a differentiation checkpoint in muscle cells in response to DNA-damaging agents (Nature Genetics, 4 November 2002; DOI:10.1038/ng1023).

Treatment of the C2C12 myoblast cell line with different genotoxic drugs (cisplatin, etoposide, or methyl methane sulfate, MMS) blocked the progression of myogenic differentiation and induced cell cycle arrest. Cisplatin and MMS prevented the transcriptional activity of the myogenic factor MyoD. This inhibition involved the c-Abl tyrosine kinase, but not the p53 or c-Jun proteins that have also been implicated in the DNA-damage response. Puri et al. show that MyoD is a direct target of the c-Abl kinase and that phosphorylation of MyoD is critical for inhibition by genotoxic drugs.