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

Oncogene. 1999 Jan 7;18(1):249-56. doi: 10.1038/sj.onc.1202257.


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 chkl 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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Ataxia Telangiectasia*
  • Cell Line, Transformed
  • Cell Survival
  • Checkpoint Kinase 1
  • Chromosome Aberrations
  • Cloning, Molecular
  • G2 Phase*
  • Gene Expression
  • Humans
  • Mitosis*
  • Protein Kinases / genetics
  • Protein Kinases / metabolism*
  • Radiation Tolerance*
  • S Phase
  • Schizosaccharomyces / enzymology*
  • Schizosaccharomyces pombe Proteins
  • Signal Transduction


  • Schizosaccharomyces pombe Proteins
  • Protein Kinases
  • CHEK1 protein, human
  • Checkpoint Kinase 1
  • Chk1 protein, S pombe