Caenorhabditis elegans cyclin B3 is required for multiple mitotic processes including alleviation of a spindle checkpoint-dependent block in anaphase chromosome segregation

PLoS Genet. 2010 Nov 24;6(11):e1001218. doi: 10.1371/journal.pgen.1001218.

Abstract

The master regulators of the cell cycle are cyclin-dependent kinases (Cdks), which influence the function of a myriad of proteins via phosphorylation. Mitotic Cdk1 is activated by A-type, as well as B1- and B2-type, cyclins. However, the role of a third, conserved cyclin B family member, cyclin B3, is less well defined. Here, we show that Caenorhabditis elegans CYB-3 has essential and distinct functions from cyclin B1 and B2 in the early embryo. CYB-3 is required for the timely execution of a number of cell cycle events including completion of the MII meiotic division of the oocyte nucleus, pronuclear migration, centrosome maturation, mitotic chromosome condensation and congression, and, most strikingly, progression through the metaphase-to-anaphase transition. Our experiments reveal that the extended metaphase delay in CYB-3-depleted embryos is dependent on an intact spindle assembly checkpoint (SAC) and results in salient defects in the architecture of holocentric metaphase chromosomes. Furthermore, genetically increasing or decreasing dynein activity results in the respective suppression or enhancement of CYB-3-dependent defects in cell cycle progression. Altogether, these data reveal that CYB-3 plays a unique, essential role in the cell cycle including promoting mitotic dynein functionality and alleviation of a SAC-dependent block in anaphase chromosome segregation.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Anaphase*
  • Animals
  • Caenorhabditis elegans / cytology*
  • Caenorhabditis elegans / embryology
  • Caenorhabditis elegans / metabolism*
  • Caenorhabditis elegans Proteins / metabolism*
  • Cell Nucleus / metabolism
  • Chromosome Segregation*
  • Cyclin B / metabolism*
  • Cytoplasmic Dyneins / metabolism
  • Embryo, Nonmammalian / cytology
  • Embryo, Nonmammalian / metabolism
  • Gene Deletion
  • Kinetochores / metabolism
  • Metaphase
  • RNA Interference
  • Spindle Apparatus / metabolism*
  • Time Factors

Substances

  • CYB-3 protein, C elegans
  • Caenorhabditis elegans Proteins
  • Cyclin B
  • Cytoplasmic Dyneins
  • DHC-1 protein, C elegans