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A direct role of M ad1 in the spindle assembly checkpoint beyond M ad2 kinetochore recruitment
Author(s) -
Kruse Thomas,
Larsen Marie Sofie Yoo,
Sedgwick Garry G,
Sigurdsson Jón Otti,
Streicher Werner,
Olsen Jesper V,
Nilsson Jakob
Publication year - 2014
Publication title -
embo reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.584
H-Index - 184
eISSN - 1469-3178
pISSN - 1469-221X
DOI - 10.1002/embr.201338101
Subject(s) - microbiology and biotechnology , chemistry , biology
The spindle assembly checkpoint ( SAC ) ensures accurate chromosome segregation by delaying entry into anaphase until all sister chromatids have become bi‐oriented. A key component of the SAC is the M ad2 protein, which can adopt either an inactive open ( O ‐ M ad2) or active closed ( C ‐ M ad2) conformation. The conversion of O ‐ M ad2 into C ‐ M ad2 at unattached kinetochores is thought to be a key step in activating the SAC . The “template model” proposes that this is achieved by the recruitment of soluble O ‐ M ad2 to C ‐ M ad2 bound at kinetochores through its interaction with M ad1. Whether M ad1 has additional roles in the SAC beyond recruitment of C ‐ M ad2 to kinetochores has not yet been addressed. Here, we show that M ad1 is required for mitotic arrest even when C ‐ M ad2 is artificially recruited to kinetochores, indicating that it has indeed an additional function in promoting the checkpoint. The C ‐terminal globular domain of M ad1 and conserved residues in this region are required for this unexpected function of M ad1.