DNA-replication/DNA-damage-dependent centrosome inactivation in Drosophila embryos

Nat Cell Biol. 2000 Feb;2(2):90-5. doi: 10.1038/35000041.

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.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Aphidicolin / pharmacology
  • Centrosome / physiology*
  • Chromosome Aberrations
  • DNA Damage*
  • DNA Replication*
  • Drosophila / embryology*
  • Drosophila / genetics
  • Mitosis / genetics*
  • Mutagens / pharmacology
  • Mutation
  • Spindle Apparatus / pathology
  • Tubulin

Substances

  • Mutagens
  • Tubulin
  • Aphidicolin