Aurora B kinase cooperates with CENP-E to promote timely anaphase onset

Chromosoma. 2010 Aug;119(4):405-13. doi: 10.1007/s00412-010-0265-x. Epub 2010 Mar 31.

Abstract

Error-free chromosome segregation requires that all chromosomes biorient on the mitotic spindle. The motor protein Centromere-associated protein E (CENP-E) facilitates chromosome congression by mediating the lateral sliding of sister chromatids along existing K-fibers, while the mitotic kinase Aurora B detaches kinetochore-microtubule interactions that are not bioriented. Whether these activities cooperate to promote efficient chromosome biorientation and timely anaphase onset is not known. We here show that the chromosomes that fail to congress after CENP-E depletion displayed high centromeric Aurora B kinase activity. This activity destabilized spindle pole proximal kinetochore-microtubule interactions resulting in a checkpoint-dependent mitotic delay that allowed CENP-E-independent chromosome congression, thus reducing chromosome segregation errors. This shows that Aurora B keeps the mitotic checkpoint active by destabilizing kinetochore fibers of polar chromosomes to permit chromosome congression in CENP-E-compromised cells and implies that this kinase normally prevents pole proximal syntelic attachments to allow CENP-E-mediated congression of mono-oriented chromosomes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anaphase / physiology*
  • Aurora Kinase B
  • Aurora Kinases
  • Chromosomal Proteins, Non-Histone / metabolism*
  • Chromosome Segregation / physiology*
  • Chromosomes, Human / physiology*
  • HeLa Cells
  • Humans
  • Kinetochores / metabolism
  • Microscopy, Fluorescence / methods
  • Microtubules / metabolism
  • Mitosis
  • Protein Serine-Threonine Kinases / metabolism*
  • RNA, Small Interfering
  • Spindle Apparatus / metabolism

Substances

  • Chromosomal Proteins, Non-Histone
  • RNA, Small Interfering
  • centromere protein E
  • AURKB protein, human
  • Aurora Kinase B
  • Aurora Kinases
  • Protein Serine-Threonine Kinases