Drosophila checkpoint kinase 2 couples centrosome function and spindle assembly to genomic integrity

Saeko Takada, Anju Kelkar, William E. Theurkauf

Research output: Contribution to journalArticlepeer-review

169 Scopus citations

Abstract

In syncytial Drosophila embryos, damaged or incompletely replicated DNA triggers centrosome disruption in mitosis, leading to defects in spindle assembly and anaphase chromosome segregation. The damaged nuclei drop from the cortex and are not incorporated into the cells that form the embryo proper. A null mutation in the Drosophila checkpoint kinase 2 tumor suppressor homolog (DmChk2) blocks this mitotic response to DNA lesions and also prevents loss of defective nuclei from the cortex. In addition, DNA damage leads to increased DmChk2 localization to the centrosome and spindle microtubules. DmChk2 is therefore essential for a "mitotic catastrophe" signal that disrupts centrosome function in response to genotoxic stress and ensures that mutant and aneuploid nuclei are eliminated from the embryonic precursor pool.

Original languageEnglish (US)
Pages (from-to)87-99
Number of pages13
JournalCell
Volume113
Issue number1
DOIs
StatePublished - Apr 4 2003

Bibliographical note

Funding Information:
We gratefully acknowledge M. Brodsky, K. Golic, and G. Rubin for kindly providing mnk , mnk -rescue, mnk,grp double, and p53 mutant flies. We also gratefully thank I. Oishi for kindly providing anti-Dmnk-L antibody, R. Saint for GFP-histone flies, A. Creighton for ICRF-193, and Bristol-Myers Squibb for VM-26. We thank B. Benoit, B.J. Cha, and B. Koppetsch for critical reading of the manuscript, and the members of the Theurkauf and Doxsey labs for helpful discussions during the course of the work. Supported by Grant Number GM50898 from the National Institute of General Medical Sciences, National Institutes for Heath. The contents of this work are solely the responsibility of the authors and do not necessarily represent the official views of the National Institute of General Medical Sciences or NIH.

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