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Chk1 complements the G2/M checkpoint defect and radiosensitivity of ataxia-telangiectasia cells

Oncogene volume 18, pages 249–256 (1999)Cite this article

Abstract

Cells from patients with the human genetic disorder ataxia-telangiectasia (A-T) are defective in the activation of cell cycle checkpoints in response to ionizing radiation damage. In order to understand the role of ATM in checkpoint control we investigated whether Schizosaccaromyces pombe chk1, a protein kinase implicated in controlling the G2 DNA damage checkpoint, might alter the radiosensitive phenotype in A-T cells. The fission yeast chk1 gene was cloned into an EBV-based vector under the control of a metallothionein promoter and transfected into A-T lymphoblastoid cells. Induction of chk1 enhanced the survival of an A-T cell line in response to radiation exposure as determined by cell viability and reduction of radiation-induced chromosome aberrations. This can be accounted for at least in part by the restoration of the G2 checkpoint to chk1 expressing cells. There was no evidence that chk1 expression corrected either the G1/S checkpoint or radioresistant DNA synthesis in S phase in these cells. These results suggest that chk1 when overexpressed acts downstream from ATM to restore the G2 checkpoint in these cells and correct the radiosensitive phenotype. These data allow us to dissociate individual checkpoint events and relate them to the radiosensitive phenotype in A-T cells.

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Acknowledgements

We wish to thank the Australian National Health and Medical Research Council, the National Institutes of Health USA and the Tzu Chi Foundation for support. Aine Farrell is acknowledged for cell culture work and Ann Knight for word-processing.

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Author notes

  1. Philip Chen and Magtouf Gatei: P Chen and M Gatei contributed equally to this work

Authors and Affiliations

  1. The Queensland Institute of Medical Research, PO Royal Brisbane Hospital, Herston, 4029, Brisbane, Australia

    Philip Chen, Magtouf Gatei, Kum Kum Khanna, Shaun P Scott, Karen Hobson & Martin F Lavin

  2. Peter MacCallum Research Institute, St. Andrews Place, East Melbourne, 3002, Victoria, Australia

    Matthew J O'Connell, Sarah J Bugg & Annette Hogg

  3. Department of Genetics, University of Melbourne, Parkville, 3052, Victoria, Australia

    Matthew J O'Connell

  4. The Department of Surgery, University of Queensland, Royal Brisbane Hospital, Herston, 4029, Brisbane, Australia

    Martin F Lavin

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Chen, P., Gatei, M., O'Connell, M. et al. Chk1 complements the G2/M checkpoint defect and radiosensitivity of ataxia-telangiectasia cells. Oncogene 18, 249–256 (1999). https://doi.org/10.1038/sj.onc.1202257

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