BUB-1 promotes amphitelic chromosome biorientation via multiple activities at the kinetochore

Elife. 2018 Dec 14;7:e40690. doi: 10.7554/eLife.40690.

Abstract

Accurate chromosome segregation relies on bioriented amphitelic attachments of chromosomes to microtubules of the mitotic spindle, in which sister chromatids are connected to opposite spindle poles. BUB-1 is a protein of the Spindle Assembly Checkpoint (SAC) that coordinates chromosome attachment with anaphase onset. BUB-1 is also required for accurate sister chromatid segregation independently of its SAC function, but the underlying mechanism remains unclear. Here we show that, in Caenorhabditis elegans embryos, BUB-1 accelerates the establishment of non-merotelic end-on kinetochore-microtubule attachments by recruiting the RZZ complex and its downstream partner dynein-dynactin at the kinetochore. In parallel, BUB-1 limits attachment maturation by the SKA complex. This activity opposes kinetochore-microtubule attachment stabilisation promoted by CLS-2CLASP-dependent kinetochore-microtubule assembly. BUB-1 is therefore a SAC component that coordinates the function of multiple downstream kinetochore-associated proteins to ensure accurate chromosome segregation.

Keywords: C. elegans; cell biology; cell division; chromosome segregation; kinetochore; microtubule; mitosis; spindle.

Publication types

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

MeSH terms

  • Anaphase*
  • Animals
  • Caenorhabditis elegans / genetics
  • Caenorhabditis elegans / metabolism
  • Caenorhabditis elegans Proteins / genetics*
  • Caenorhabditis elegans Proteins / metabolism
  • Chromosome Segregation*
  • Dynactin Complex / genetics
  • Dynactin Complex / metabolism
  • Dyneins / genetics
  • Dyneins / metabolism
  • Embryo, Nonmammalian
  • Gene Expression Regulation
  • Kinetochores / metabolism*
  • Kinetochores / ultrastructure
  • M Phase Cell Cycle Checkpoints*
  • Microtubule-Associated Proteins / genetics
  • Microtubule-Associated Proteins / metabolism
  • Microtubules / metabolism
  • Microtubules / ultrastructure
  • Protein-Serine-Threonine Kinases / genetics*
  • Protein-Serine-Threonine Kinases / metabolism
  • Signal Transduction
  • Spindle Apparatus / metabolism*
  • Spindle Apparatus / ultrastructure

Substances

  • CLS-2 protein, C elegans
  • Caenorhabditis elegans Proteins
  • Dynactin Complex
  • Microtubule-Associated Proteins
  • Protein-Serine-Threonine Kinases
  • bub-1 protein, C elegans
  • Dyneins