The Aurora-B-dependent NoCut checkpoint prevents damage of anaphase bridges after DNA replication stress

Nat Cell Biol. 2016 May;18(5):516-26. doi: 10.1038/ncb3343. Epub 2016 Apr 25.

Abstract

Anaphase chromatin bridges can lead to chromosome breakage if not properly resolved before completion of cytokinesis. The NoCut checkpoint, which depends on Aurora B at the spindle midzone, delays abscission in response to chromosome segregation defects in yeast and animal cells. How chromatin bridges are detected, and whether abscission inhibition prevents their damage, remain key unresolved questions. We find that bridges induced by DNA replication stress and by condensation or decatenation defects, but not dicentric chromosomes, delay abscission in a NoCut-dependent manner. Decatenation and condensation defects lead to spindle stabilization during cytokinesis, allowing bridge detection by Aurora B. NoCut does not prevent DNA damage following condensin or topoisomerase II inactivation; however, it protects anaphase bridges and promotes cellular viability after replication stress. Therefore, the molecular origin of chromatin bridges is critical for activation of NoCut, which plays a key role in the maintenance of genome stability after replicative stress.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actomyosin / metabolism
  • Adenosine Triphosphatases / metabolism
  • Anaphase* / drug effects
  • Aurora Kinases / metabolism*
  • Cell Cycle Checkpoints* / drug effects
  • Chromatin / metabolism
  • Chromosomal Proteins, Non-Histone / metabolism
  • DNA Replication* / drug effects
  • DNA Topoisomerases, Type II / metabolism
  • DNA-Binding Proteins / metabolism
  • Histone Acetyltransferases / metabolism
  • Hydroxyurea / pharmacology
  • Microbial Viability / drug effects
  • Models, Biological
  • Multiprotein Complexes / metabolism
  • Saccharomyces cerevisiae / cytology*
  • Saccharomyces cerevisiae / drug effects
  • Saccharomyces cerevisiae / metabolism*
  • Saccharomyces cerevisiae / ultrastructure
  • Saccharomyces cerevisiae Proteins / metabolism*
  • Spindle Apparatus / drug effects
  • Spindle Apparatus / metabolism
  • Stress, Physiological* / drug effects

Substances

  • AHC1 protein, S cerevisiae
  • Chromatin
  • Chromosomal Proteins, Non-Histone
  • DNA-Binding Proteins
  • Multiprotein Complexes
  • Saccharomyces cerevisiae Proteins
  • condensin complexes
  • Actomyosin
  • Histone Acetyltransferases
  • Aurora Kinases
  • IPL1 protein, S cerevisiae
  • Adenosine Triphosphatases
  • DNA Topoisomerases, Type II
  • Hydroxyurea