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DNA damage induces Chk1‐dependent centrosome amplification
Author(s) -
Bourke Emer,
Dodson Helen,
Merdes Andreas,
Cuffe Lorraine,
Zachos George,
Walker Mark,
Gillespie David,
Morrison Ciaran G
Publication year - 2007
Publication title -
embo reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.584
H-Index - 184
eISSN - 1469-3178
pISSN - 1469-221X
DOI - 10.1038/sj.embor.7400962
Subject(s) - centrosome , chek1 , dna damage , microbiology and biotechnology , biology , ataxia telangiectasia , g2 m dna damage checkpoint , kinase , dna , genetics , cell , cell cycle , cell cycle checkpoint
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.