Ku affects the ATM-dependent S phase checkpoint following ionizing radiation Journal Article


Authors: Zhou, X. Y.; Wang, X.; Wang, H. Y.; Chen, D. J.; Li, G. C.; Iliakis, G.; Wang, Y.
Article Title: Ku affects the ATM-dependent S phase checkpoint following ionizing radiation
Abstract: Following exposure to genotoxic stress, proliferating cells actively slow down DNA replication through an S phase checkpoint to provide time for repair. The ATM-dependent pathway plays an important role in the S phase checkpoint response following ionizing irradiation. We report that there is a stronger S phase checkpoint response in irradiated Ku80(-/-) cells as compared with their wild-type counterparts, which has no relationship to DNA-dependent protein kinase (DNA-PK) activity but correlates with a higher ATM activity and with more ATM bound to chromatin DNA in such cells. Wortmannin, a nonspecific inhibitor of ATM, not only reduces the higher activity of ATM kinase, but also abolishes the stronger S phase checkpoint response in Ku80(-/-) cells. Furthermore, a specific ATM antisense oligonucleotide abolishes the stronger S checkpoint response in Ku80(-/-) cells and renders these cells practically indistinguishable from Ku80(+/+) cells for this endpoint. These results in aggregate indicate that the stronger S checkpoint in irradiated Ku80(-/-) cells is due to the higher ATM kinase activity.
Keywords: ionizing radiation; repair; double-strand breaks; atm; recombination; damage; cells; sensitivity; ataxia-telangiectasia; involvement; protein-kinase; ku; v(d)j; s phase checkpoint; dna end binding
Journal Title: Oncogene
Volume: 21
Issue: 41
ISSN: 0950-9232
Publisher: Nature Publishing Group  
Date Published: 2002-09-12
Start Page: 6377
End Page: 6381
Language: English
ACCESSION: WOS:000177829000014
DOI: 10.1038/sj.onc.1205782
PROVIDER: wos
PUBMED: 12214278
Notes: Article -- Source: Wos
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  1. Gloria C Li
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