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

Xiang Yang Zhou, Xiang Wang, Hongyan Wang, David J. Chen, Gloria C. Li, George Iliakis, Ya Wang

Research output: Contribution to journalArticle

23 Scopus citations

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-depeudeut 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.

Original languageEnglish (US)
Pages (from-to)6377-6381
Number of pages5
JournalOncogene
Volume21
Issue number41
DOIs
StatePublished - Jan 1 2002

Keywords

  • ATM
  • Ionizing radiation
  • Ku
  • S phase checkpoint

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cancer Research

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  • Cite this

    Zhou, X. Y., Wang, X., Wang, H., Chen, D. J., Li, G. C., Iliakis, G., & Wang, Y. (2002). Ku affects the ATM-dependent S phase checkpoint following ionizing radiation. Oncogene, 21(41), 6377-6381. https://doi.org/10.1038/sj.onc.1205782