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 language | English (US) |
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Pages (from-to) | 6377-6381 |
Number of pages | 5 |
Journal | Oncogene |
Volume | 21 |
Issue number | 41 |
DOIs | |
State | Published - 2002 |
Keywords
- ATM
- Ionizing radiation
- Ku
- S phase checkpoint
ASJC Scopus subject areas
- Molecular Biology
- Genetics
- Cancer Research