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  • Original Paper
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p53 inhibits entry into mitosis when DNA synthesis is blocked

Oncogene volume 18, pages 283–295 (1999)Cite this article

Abstract

Human and mouse fibroblasts with normal p53 fail to enter mitosis when DNA synthesis is blocked by aphidicolin or hydroxyurea. Isogenic p53-null fibroblasts do enter mitosis with incompletely replicated DNA, revealing that p53 contributes to a checkpoint that ensures that mitosis does not occur until DNA synthesis is complete. When treated with N-(phosphonacetyl)-L-aspartate (PALA), which inhibits pyrimidine nucleotide synthesis, leading to synthesis of damaged DNA from highly unbalanced dNTP pools, p53-null cells enter mitosis after they have completed DNA replication, but cells with wild-type p53 do not, revealing that p53 also mediates a checkpoint that monitors the quality of newly replicated DNA.

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Acknowledgements

We gratefully acknowledge gifts of p53-null MEFs from L Donehower (Baylor College of Medicine), MDAH041 cells from M Tainsky (MD Anderson Cancer Center), and antiserum against pH1b from CD Allis (Syracuse University). We also thank Pamela Duncan for technical assistance and Teresa Bendele for assistance with the FACScan analyses. WRT is a Terry Fox Research Fellow supported by funds provided by the Terry Fox Run. This work was supported by grant GM-49345 from the National Institutes of Health.

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  1. Department of Molecular Biology, Lerner Research Institute, The Cleveland Clinic Foundation, 9500 Euclid Avenue, Cleveland, 44195, Ohio, USA

    William R Taylor, Munna L Agarwal, Archana Agarwal, Dennis W Stacey & George R Stark

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Taylor, W., Agarwal, M., Agarwal, A. et al. p53 inhibits entry into mitosis when DNA synthesis is blocked. Oncogene 18, 283–295 (1999). https://doi.org/10.1038/sj.onc.1202516

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