title: DNA-replication/DNA-damage-dependent centrosome inactivation in Drosophila embryos.
abstract: During early embryogenesis of Drosophila melanogaster, mutations in the DNA-replication checkpoint lead to chromosome-segregation failures. Here we show that these segregation failures are associated with the assembly of an anastral microtubule spindle, a mitosis-specific loss of centrosome function, and dissociation of several components of the gamma-tubulin ring complex from a core centrosomal structure. The DNA-replication inhibitor aphidicolin and DNA-damaging agents trigger identical mitotic defects in wild-type embryos, indicating that centrosome inactivation is a checkpoint-independent and mitosis-specific response to damaged or incompletely replicated DNA. We propose that centrosome inactivation is part of a damage-control system that blocks chromosome segregation when replication/damage checkpoint control fails.
authors.affiliation: Department of Radiobiology, Faculty of Medicine, University of Groningen, Groningen, The Netherlands.
authors.forename: O C
authors.initials: OC
authors.lastname: Sibon
authors.forename: A
authors.initials: A
authors.lastname: Kelkar
authors.forename: W
authors.initials: W
authors.lastname: Lemstra
authors.forename: W E
authors.initials: WE
authors.lastname: Theurkauf
mesh_terms: D000818:Animals; D016590:Aphidicolin / Q000494:pharmacology; D018385:Centrosome / Q000502:physiology*; D002869:Chromosome Aberrations; D004249:DNA Damage; D004261:DNA Replication; D004330:Drosophila / Q000196:embryology* / Q000235:genetics; D008938:Mitosis / Q000235:genetics*; D009153:Mutagens / Q000494:pharmacology; D009154:Mutation; D008941:Spindle Apparatus / Q000473:pathology; D014404:Tubulin
chemical_list: D009153:Mutagens; D014404:Tubulin; D016590:Aphidicolin