A direct role of Mad1 in the spindle assembly checkpoint beyond Mad2 kinetochore recruitment

TY - JOUR

T1 - A direct role of Mad1 in the spindle assembly checkpoint beyond Mad2 kinetochore recruitment

AU - Kruse, Thomas

AU - Larsen, Marie Sofie Yoo

AU - Sedgwick, Garry G

AU - Sigurdsson, Jón Otti

AU - Streicher, Werner

AU - Olsen, Jesper Velgaard

AU - Nilsson, Jakob

PY - 2014/3

Y1 - 2014/3

N2 - 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 Mad2 protein, which can adopt either an inactive open (O-Mad2) or active closed (C-Mad2) conformation. The conversion of O-Mad2 into C-Mad2 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-Mad2 to C-Mad2 bound at kinetochores through its interaction with Mad1. Whether Mad1 has additional roles in the SAC beyond recruitment of C-Mad2 to kinetochores has not yet been addressed. Here, we show that Mad1 is required for mitotic arrest even when C-Mad2 is artificially recruited to kinetochores, indicating that it has indeed an additional function in promoting the checkpoint. The C-terminal globular domain of Mad1 and conserved residues in this region are required for this unexpected function of Mad1.

AB - 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 Mad2 protein, which can adopt either an inactive open (O-Mad2) or active closed (C-Mad2) conformation. The conversion of O-Mad2 into C-Mad2 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-Mad2 to C-Mad2 bound at kinetochores through its interaction with Mad1. Whether Mad1 has additional roles in the SAC beyond recruitment of C-Mad2 to kinetochores has not yet been addressed. Here, we show that Mad1 is required for mitotic arrest even when C-Mad2 is artificially recruited to kinetochores, indicating that it has indeed an additional function in promoting the checkpoint. The C-terminal globular domain of Mad1 and conserved residues in this region are required for this unexpected function of Mad1.

U2 - 10.1002/embr.201338101

DO - 10.1002/embr.201338101

M3 - Journal article

C2 - 24477933

SN - 1469-221X

VL - 15

SP - 282

EP - 290

JO - E M B O Reports

JF - E M B O Reports

ER -