Muscle checkpoint

Cell-cycle checkpoints ensure that damaged DNA is repaired prior to cell division. In an Advanced Online Publication in Nature Genetics, Puri et al. describe characterization of a differentiation checkpoint that operates 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 sulphate, 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 involves 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.