Drosophila checkpoint kinase 2 couples centrosome function and spindle assembly to genomic integrity.
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.
Takada
Saeko
S
Program in Molecular Medicine, University of Massachusetts Medical School, 373 Plantation Street, Worcester, MA 01605, USA.
Kelkar
Anju
A
Theurkauf
William E
WE
D000782:Aneuploidy; D000818:Animals; D002467:Cell Nucleus / Q000201:enzymology / Q000235:genetics; D002471:Cell Transformation, Neoplastic / Q000235:genetics; D018385:Centrosome / Q000378:metabolism*; D064447:Checkpoint Kinase 2; D004249:DNA Damage / Q000187:drug effects / Q000235:genetics*; D004261:DNA Replication / Q000235:genetics; D026942:DNA Topoisomerases / Q000235:genetics / Q000378:metabolism; D029721:Drosophila Proteins; D004331:Drosophila melanogaster / Q000196:embryology* / Q000201:enzymology / Q000235:genetics; D004625:Embryo, Nonmammalian / Q000196:embryology / Q000201:enzymology; D005260:Female; D016678:Genome; D008297:Male; D008938:Mitosis / Q000235:genetics*; D008954:Models, Biological; D009154:Mutation / Q000235:genetics*; D017346:Protein Serine-Threonine Kinases / Q000172:deficiency* / Q000235:genetics; D008941:Spindle Apparatus / Q000235:genetics / Q000378:metabolism*; D013234:Stem Cells / Q000201:enzymology; D059003:Topoisomerase Inhibitors
D029721:Drosophila Proteins; D059003:Topoisomerase Inhibitors; D064447:Checkpoint Kinase 2; D017346:Protein Serine-Threonine Kinases; C112435:lok protein, Drosophila; D026942:DNA Topoisomerases