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The Spindle Assembly Checkpoint

The Spindle Assembly Checkpoint

The spindle assembly checkpoint is a molecular surveillance mechanism ensuring the fidelity of chromosome segregation during anaphase. The checkpoint monitors the completion of all the prerequisite steps before chromosome segregation to determine whether the segregation process should proceed or be delayed.
Many proteins function together to control the spindle assembly checkpoint. Mutations affecting these proteins may allow cells to proceed into anaphase prematurely, resulting in the...

The Spindle Assembly Checkpoint

The Spindle Assembly Checkpoint

The spindle assembly checkpoint is a molecular surveillance mechanism ensuring the fidelity of chromosome segregation during anaphase. The checkpoint monitors the completion of all the prerequisite steps before chromosome segregation to determine whether the segregation process should proceed or be delayed.
Many proteins function together to control the spindle assembly checkpoint. Mutations affecting these proteins may allow cells to proceed into anaphase prematurely, resulting in the...

The Mitotic Spindle

The Mitotic Spindle

The mitotic spindle—or spindle apparatus—is a eukaryotic, cytoskeletal structure made up of long protein fibers called microtubules. Formed during cell division, the spindle separates sister chromatids and moves them to opposite ends of a parental cell, where the now individual chromosomes are distributed to two daughter cell nuclei.
The bipolar configuration of the mitotic spindle facilitates chromosomal segregation, preparing the cell for division. One mechanism that ensures bipolar mitotic...

The Mitotic Spindle

The Mitotic Spindle

The mitotic spindle—or spindle apparatus—is a eukaryotic, cytoskeletal structure made up of long protein fibers called microtubules. Formed during cell division, the spindle separates sister chromatids and moves them to opposite ends of a parental cell, where the now individual chromosomes are distributed to two daughter cell nuclei.
The bipolar configuration of the mitotic spindle facilitates chromosomal segregation, preparing the cell for division. One mechanism that ensures bipolar mitotic...

Spindle Assembly

Spindle Assembly

Spindle assembly occurs through three, often coexisting, pathways – the centrosome-mediated pathway, the chromatin-mediated pathway, and the microtubule-mediated pathway – collectively contributing to form a robust spindle apparatus.
In most cells, centrosomes are the primary microtubule nucleation centers. In the centrosome-mediated pathway, the G2-prophase transition triggers centrosome maturation and increased microtubule nucleation. Progressive nucleation results in a microtubule array...

Separation of Sister Chromatids

Separation of Sister Chromatids

At the transition from prophase to metaphase, there is a reduction in cohesion along the chromosomal arms, resulting in the resolution of sister chromatids. However, residual cohesin connections remain to hold the sister chromatids together until the transition from metaphase to anaphase. The residual connection prevents any premature separation of sister chromatids, blocking the risks of aneuploidy within the daughter cells.
At the onset of anaphase, separase, a proteolytic enzyme, is...

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Related Experiment Video

Updated: Jul 10, 2026

Evaluation of the Spindle Assembly Checkpoint Integrity in Mouse Oocytes

Evaluation of the Spindle Assembly Checkpoint Integrity in Mouse Oocytes

Published on: September 13, 2022

The Mad2 conformational dimer: structure and implications for the spindle assembly checkpoint.

Marina Mapelli¹, Lucia Massimiliano, Stefano Santaguida

¹Department of Experimental Oncology, European Institute of Oncology, Via Adamello 16, I-20139, Milan, Italy. marina.mapelli@ifom-ieo-campus.it

|November 21, 2007

Summary

The Mad2 protein regulates cell division by forming a unique dimer. This crystal structure reveals how open and closed Mad2 conformers selectively bind, crucial for preventing chromosome errors during mitosis.

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Area of Science:

Cell Biology
Molecular Biology
Structural Biology

Background:

Mad2 protein is essential for the spindle assembly checkpoint, preventing errors in chromosome segregation during mitosis.
Mad2 exhibits two distinct conformations (open and closed) and forms specific interactions with Mad1 and Cdc20.
A conformational dimer of open (O-Mad2) and closed (C-Mad2) Mad2 is vital for spindle checkpoint function across species.

Purpose of the Study:

To determine the crystal structure of the O-Mad2-C-Mad2 conformational dimer.
To elucidate the structural basis for the selective dimerization of O-Mad2 and C-Mad2 conformers.
To understand the role of Mad2 conformational changes in spindle checkpoint regulation.

Main Methods:

X-ray crystallography to obtain the structure of the O-Mad2-C-Mad2 conformational dimer.
Structural analysis to identify the dimerization interface and key residues.
Correlating structural findings with Mad2's topological changes and function.

Main Results:

The crystal structure reveals an asymmetric interface responsible for the selective dimerization of O-Mad2 and C-Mad2.
Identification of buried hydrophobic residues whose rearrangement is linked to Mad2's topological transition.
The dimer structure supports a catalytic model for Mad2 function in the spindle checkpoint.

Conclusions:

The O-Mad2-C-Mad2 dimer structure provides critical insights into spindle assembly checkpoint mechanisms.
Structural data explains the selective interaction between Mad2 conformers, essential for checkpoint fidelity.
The findings support a model where C-Mad2 acts as a template to facilitate O-Mad2 binding to Cdc20, ensuring accurate chromosome segregation.