Document Detail

Defect in multiple cell cycle checkpoints in ataxia-telangiectasia postirradiation.
MedLine Citation:
PMID:  8702789     Owner:  NLM     Status:  MEDLINE    
The recent description of a novel gene (ATM) mutated in ataxia-telangiectasia (A-T), with homologies to genes encoding proteins involved in both G1/S and G2/M checkpoint control, points to a common defect in cell cycle control in A-T operating through the cyclin-dependent kinases. In this report we demonstrate that cyclin-dependent kinases are resistant to inhibition by ionizing radiation exposure in A-T cells, and this appears to be due to insufficient induction of WAF1. Exposure of control lymphoblastoid cells to radiation during S phase and in G2 phase causes a rapid inhibition of cyclin A-Cdk2 and cyclin B-Cdc2 activities, respectively. Irradiation led to a 5-20-fold increase in Cdk-associated WAF1 in these cells, which accounts at least in part for the decrease in cyclin-dependent kinase activity. In contrast, radiation did not inhibit any of the cyclin-dependent kinase activities in S phase or G2 phase in A-T cells at short times after irradiation nor was there any significant change in the level of Cdk-associated WAF1 compared to unirradiated cells. These results are similar to those reported previously for the G1 checkpoint and provide additional evidence for the involvement of ATM at multiple points in cell cycle regulation.
H Beamish; R Williams; P Chen; M F Lavin
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  The Journal of biological chemistry     Volume:  271     ISSN:  0021-9258     ISO Abbreviation:  J. Biol. Chem.     Publication Date:  1996 Aug 
Date Detail:
Created Date:  1996-10-11     Completed Date:  1996-10-11     Revised Date:  2012-06-25    
Medline Journal Info:
Nlm Unique ID:  2985121R     Medline TA:  J Biol Chem     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  20486-93     Citation Subset:  IM    
Queensland Cancer Fund Research Unit, Queensland Institute of Medical Research, Bancroft Centre, 300 Herston Road, Brisbane, Queensland 4029, Australia.
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MeSH Terms
Ataxia Telangiectasia / metabolism,  pathology*
CDC2-CDC28 Kinases*
Cell Cycle
Cells, Cultured
Cyclin-Dependent Kinase 2
Cyclin-Dependent Kinase Inhibitor p21
Cyclin-Dependent Kinases / metabolism
Cyclins / metabolism
DNA Repair*
Phosphotyrosine / metabolism
Protein-Serine-Threonine Kinases / metabolism
S Phase / radiation effects
Reg. No./Substance:
0/CDKN1A protein, human; 0/Cyclin-Dependent Kinase Inhibitor p21; 0/Cyclins; 21820-51-9/Phosphotyrosine; EC Kinases; EC Kinases; EC protein, human; EC Kinase 2; EC Kinases

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