Chromosoma

, Volume 121, Issue 5, pp 509–525 | Cite as

Connecting up and clearing out: how kinetochore attachment silences the spindle assembly checkpoint

Review

Abstract

With the goal of creating two genetically identical daughter cells, cell division culminates in the equal segregation of sister chromatids. This phase of cell division is monitored by a cell cycle checkpoint known as the spindle assembly checkpoint (SAC). The SAC actively prevents chromosome segregation while one or more chromosomes, or more accurately kinetochores, remain unattached to the mitotic spindle. Such unattached kinetochores recruit SAC proteins to assemble a diffusible anaphase inhibitor. Kinetochores stop production of this inhibitor once microtubules (MTs) of the mitotic spindle are bound, but productive attachment of all kinetochores is required to satisfy the SAC, initiate anaphase, and exit from mitosis. Although mechanisms of kinetochore signaling and SAC inhibitor assembly and function have received the bulk of attention in the past two decades, recent work has focused on the principles of SAC silencing. Here, we review the mechanisms that silence SAC signaling at the kinetochore, and in particular, how attachment to spindle MTs and biorientation on the mitotic spindle may turn off inhibitor generation. Future challenges in this area are highlighted towards the goal of building a comprehensive molecular model of this process.

SAC

Spindle assembly checkpoint

MT

Microtubule

RZZ

Rod/Zw10/Zwilch

CENP

Centromere protein

KMN

Knl1/Mis12/Ndc80 complex

CPC

Chromosome passenger complex

TAP

Tandem affinity purification

Cdk1

Cyclin-dependent kinase 1

APC/C

Anaphase promoting complex/cyclosome

MCC

Mitotic checkpoint complex

DIC

Dynein intermediate chain

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© Springer-Verlag 2012

Authors and Affiliations

  1. 1.Department of Medical Oncology and Department of Molecular Cancer ResearchUniversity Medical Center UtrechtUtrechtThe Netherlands
  2. 2.Department of Systems Biology, Harvard Medical School and Renal DivisionBrigham and Women’s HospitalBostonUSA
  3. 3.Medical Oncology & Molecular Cancer ResearchUniversity Medical Center UtrechtUtrechtThe Netherlands
  4. 4.Department of Systems BiologyHarvard Medical SchoolBostonUSA

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