A direct role of Mad1 in the spindle assembly checkpoint beyond Mad2 kinetochore recruitment
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A direct role of Mad1 in the spindle assembly checkpoint beyond Mad2 kinetochore recruitment. / Kruse, Thomas; Larsen, Marie Sofie Yoo; Sedgwick, Garry G; Sigurdsson, Jón Otti; Streicher, Werner; Olsen, Jesper Velgaard; Nilsson, Jakob.
In: E M B O Reports, Vol. 15, 29.01.2014, p. 282-290.Research output: Contribution to journal › Journal article › Research › peer-review
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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 - 2014/1/29
Y1 - 2014/1/29
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
VL - 15
SP - 282
EP - 290
JO - E M B O Reports
JF - E M B O Reports
SN - 1469-221X
ER -
ID: 102260550