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PMID: 17468739 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

DNA damage induces Chk1-dependent centrosome amplification.

EMBO reports ·Vol. 8 ·No. 6 ·2007-06-00 ·Pages 603-9

Bourke E, Dodson H, Merdes A, Cuffe L, Zachos G, Walker M, Gillespie D, Morrison CG

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.

MeSH Terms
Animals Cell Cycle/radiation effects Cell Line Centrosome/metabolism,radiation effects Checkpoint Kinase 1 Chickens DNA Damage Humans Protein Kinases/metabolism Radiation, Ionizing
Chemicals
Protein Kinases CHEK1 protein, human Checkpoint Kinase 1
Authors & Affiliations
8 authors, click to expand affiliations / ORCID
Bourke Emer
Department of Biochemistry and NCBES, National University of Ireland-Galway, University Road, Galway, Ireland.
Dodson Helen
Merdes Andreas
Cuffe Lorraine
Zachos George
Walker Mark
Gillespie David
Morrison Ciaran G
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Article Info
Journal
EMBO reports
Abbr.
EMBO Rep
ISSN
1469-221X
DOI
10.1038/sj.embor.7400962
Published
2007-06-00
Epub
2007-00-27
Pages
603-9
Language
English
Region
England
NLM ID
100963049
PMCID
PMC2002539
Subset
IM
External Links
PubMed source DOI: 10.1038/sj.embor.7400962 PMC Full Text View journal details
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