Astral microtubule forces alter nuclear organization and inhibit DNA repair in budding yeast

Mol Biol Cell. 2019 Jul 22;30(16):2000-2013. doi: 10.1091/mbc.E18-12-0808. Epub 2019 May 8.


Dividing cells must balance the maintenance of genome integrity with the generation of cytoskeletal forces that control chromosome position. In this study, we investigate how forces on astral microtubules impact the genome during cell division by using live-cell imaging of the cytoskeleton, chromatin, and DNA damage repair in budding yeast. Our results demonstrate that dynein-dependent forces on astral microtubules are propagated through the spindle during nuclear migration and when in excess can increase the frequency of double-stranded breaks (DSBs). Under these conditions, we find that homology-directed repair of DSBs is delayed, indicating antagonism between nuclear migration and the mechanism of homology-directed repair. These effects are partially rescued by mutants that weaken pericentric cohesion or mutants that decrease constriction on the nucleus as it moves through the bud neck. We propose that minimizing nuclear movement aids in finding a donor strand for homologous recombination.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biomechanical Phenomena
  • Cell Nucleus / metabolism*
  • Chromatin / metabolism
  • DNA Breaks, Double-Stranded
  • DNA Repair*
  • Microtubules / metabolism*
  • Mutation / genetics
  • Saccharomycetales / metabolism*
  • Spindle Apparatus / metabolism


  • Chromatin