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

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 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.

journal_name

Oncogene

journal_title

Oncogene

authors

Chen P,Gatei M,O'Connell MJ,Khanna KK,Bugg SJ,Hogg A,Scott SP,Hobson K,Lavin MF

doi

10.1038/sj.onc.1202257

subject

Has Abstract

pub_date

1999-01-07 00:00:00

pages

249-56

issue

1

eissn

0950-9232

issn

1476-5594

journal_volume

18

pub_type

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