DNA damage induces Chk1‐dependent centrosome amplification
Open Access
- 27 April 2007
- journal article
- research article
- Published by Springer Nature in EMBO Reports
- Vol. 8 (6) , 603-609
- https://doi.org/10.1038/sj.embor.7400962
Abstract
Centrosomal abnormalities are frequently observed in cancers and in cells with defective DNA repair. Here, we used light and electron microscopy to show that DNA damage induces centrosome amplification, not fragmentation, in human cells. Caffeine abrogated this amplification in both ATM (ataxia telangiectasia, mutated)‐ and ATR (ATM and Rad3‐related)‐defective cells, indicating a complementary role for these DNA‐damage‐responsive kinases in promoting centrosome amplification. Inhibition of checkpoint kinase 1 (Chk1) by RNA‐mediated interference or drug treatment suppressed DNA‐damage‐induced centrosome amplification. Radiation‐induced centrosome amplification was abrogated in Chk1 −/− DT40 cells, but occurred at normal levels in Chk1 −/− cells transgenically expressing Chk1 . Expression of kinase‐dead Chk1, or Chk1S345A, through which the phosphatidylinositol‐3‐kinase cannot signal, failed to restore centrosome amplification, showing that signalling to Chk1 and Chk1 catalytic activity are necessary to promote centrosome overduplication after DNA damage.Keywords
This publication has 35 references indexed in Scilit:
- NEDD1-dependent recruitment of the γ-tubulin ring complex to the centrosome is necessary for centriole duplication and spindle assemblyThe Journal of cell biology, 2006
- ATM- and cell cycle-dependent regulation of ATR in response to DNA double-strand breaksNature Cell Biology, 2005
- Inhibition of Human Chk1 Causes Increased Initiation of DNA Replication, Phosphorylation of ATR Targets, and DNA BreakageMolecular and Cellular Biology, 2005
- Chk1-Dependent S-M Checkpoint Delay in Vertebrate Cells Is Linked to Maintenance of Viable Replication StructuresMolecular and Cellular Biology, 2005
- Centrosome number is controlled by a centrosome-intrinsic block to reduplicationNature Cell Biology, 2003
- Centrosomes Split in the Presence of Impaired DNA Integrity during MitosisMolecular Biology of the Cell, 2003
- Expression of mutant telomerase in immortal telomerase-negative human cells results in cell cycle deregulation, nuclear and chromosomal abnormalities and rapid loss of viabilityOncogene, 2001
- Radiation-Induced Centrosome Overduplication and Multiple Mitotic Spindles in Human Tumor CellsExperimental Cell Research, 2000
- Centriole distribution during tripolar mitosis in Chinese hamster ovary cells.The Journal of cell biology, 1984
- Microtubule-organizing centers abnormal in number, structure, and nucleating activity in x-irradiated mammalian cells.The Journal of cell biology, 1983