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  The Mad1/Mad2 complex as a template for Mad2 activation in the spindle assembly checkpoint

De Antoni, A., Pearson, C. G., Cimini, D., Canman, J. C., Sala, V., Nezi, L., et al. (2005). The Mad1/Mad2 complex as a template for Mad2 activation in the spindle assembly checkpoint. CURRENT BIOLOGY, 15(3), 214-225. doi:10.1016/j.cub.2005.01.038.

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 Creators:
De Antoni, Anna1, Author
Pearson, Chad G.2, Author
Cimini, Daniela2, Author
Canman, Julie C.2, Author
Sala, Valeria1, Author
Nezi, Luigi1, Author
Mapelli, Marina1, Author
Sironi, Lucia1, Author
Faretta, Mario1, Author
Salmon, Edward D.2, Author
Musacchio, Andrea3, Author           
Affiliations:
1Department of Experimental Oncology, European Institute of Oncology, Via Ripamonti 435, 20141 Milano, Italy, ou_persistent22              
2Department of Biology, University of North Carolina at Chapel Hill, 607 Fordham Hall, Chapel Hill, NC 27599 USA, ou_persistent22              
3Abt. I:Mechanistische Zellbiologie, Max Planck Institute of Molecular Physiology, Max Planck Society, ou_1753287              

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 Abstract: Background: The spindle assembly checkpoint (SAC) imparts fidelity to chromosome segregation by delaying anaphase until all sister chromatid pairs have become bipolarly attached. Mad2 is a component of the SAC effector complex that sequesters Cdc20 to halt anaphase. In prometaphase, Mad2 is recruited to kinetochores with the help of Mad1, and it is activated to bind Cdc20. These events are linked to the existence of two distinct conformers of Mad2: a closed conformer bound to its kinetochore receptor Mad1 or its target in the checkpoint Cdc20 and an open conformer unbound to these ligands. Results: We investigated the mechanism of Mad2 recruitment to the kinetochore during checkpoint activation and subsequent transfer to Cdc20. We report that a closed conformer of Mad2 constitutively bound to Mad1, rather than Mad1 itself, is the kinetochore receptor for cytosolic open Mad2 and show that the interaction of open and closed Mad2 conformers is essential to sustain the SAC. Conclusions: We propose that closed Mad2 bound to Mad1 represents a template for the conversion of open Mad2 into closed Mad2 bound to Cdc20. This simple model, which we have named the "Mad2 template" model, predicts a mechanism for cytosolic propagation of the spindle checkpoint signal away from kinetochores.

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 Dates: 2005
 Publication Status: Issued
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 Identifiers: ISI: 000227027700019
DOI: 10.1016/j.cub.2005.01.038
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Title: CURRENT BIOLOGY
Source Genre: Journal
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Pages: - Volume / Issue: 15 (3) Sequence Number: - Start / End Page: 214 - 225 Identifier: ISSN: 0960-9822