Dispensability of the SAC Depends on the Time Window Required by Aurora B to Ensure Chromosome Biorientation.

Marta Muñoz-Barrera,Isabel Aguilar,Fernando Monje-Casas

doi:10.1371/journal.pone.0144972

Abstract

Aurora B and the spindle assembly checkpoint (SAC) collaborate to ensure the proper biorientation of chromosomes during mitosis. However, lack of Aurora B activity and inactivation of the SAC have a very different impact on chromosome segregation. This is most evident in Saccharomyces cerevisiae, since in this organism the lack of Aurora B is lethal and leads to severe aneuploidy problems, while the SAC is dispensable under normal growth conditions and mutants in this checkpoint do not show evident chromosome segregation defects. We demonstrate that the efficient repair of incorrect chromosome attachments by Aurora B during the initial stages of spindle assembly in budding yeast determines the lack of chromosome segregation defects in SAC mutants, and propose that the differential time window that Aurora B kinase requires to establish chromosome biorientation is the key factor that determines why some cells are more dependent on a functional SAC than others.

Highlights

The correct distribution of the genetic material during mitosis requires the attachment of all chromosomes to spindle microtubules
Different hypotheses could be initially considered in order to explain the absence of chromosome segregation defects in spindle assembly checkpoint (SAC) mutants during the normal growth of S. cerevisiae, in contrast to the dramatic phenotype shown by yeast cells lacking Ipl1 activity
Despite several attempts to verify a putative physical interaction between Ipl1 and the anaphase-promoting complex/cyclosome (APC/C) or Cdc20 that could uncover a regulation of the metaphase to anaphase transition by Aurora B, we were unable to find any evidence of a direct association between these proteins

Summary

Introduction

The correct distribution of the genetic material during mitosis requires the attachment of all chromosomes to spindle microtubules. Aurora B kinase, the enzymatic component of the chromosome passenger complex (CPC), is crucial to achieve chromosome biorientation, and collaborates with the SAC to correct erroneous kinetochore-microtubule (KT-MT) attachments [3, 4]. A linear model has been proposed to explain the resolution of syntelic chromosomal attachments (when both sister chromatids bind microtubules emanating from the same spindle pole) by Aurora B and the SAC. According to this model, Aurora B senses incorrect attachments that originate a lack of tension in the spindle, and destabilizes these connections generating unattached kinetochores

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