TY - JOUR
T1 - Mad1 promotes chromosome congression by anchoring a kinesin motor to the kinetochore
AU - Akera, Takashi
AU - Goto, Yuhei
AU - Sato, Masamitsu
AU - Yamamoto, Masayuki
AU - Watanabe, Yoshinori
N1 - Funding Information:
We thank the Yeast Genetic Resource Center (YGRC) for yeast strains, S. Hauf for critically reading the manuscript, J. Pines (Gurdon Institute in UK) for hMad1 RNAi information and all members of the Watanabe laboratory for their support and discussion. This work was supported in part by a JSPS Research Fellowship (to T.A.) and MEXT KAKENHI Grant Number 25000014 (to Y.W.).
Publisher Copyright:
© 2015 Macmillan Publishers Limited.
PY - 2015/9/1
Y1 - 2015/9/1
N2 - For proper partitioning of genomes in mitosis, all chromosomes must be aligned at the spindle equator before the onset of anaphase. The spindle assembly checkpoint (SAC) monitors this process, generating a â € wait anaphase'signal at unattached kinetochores of misaligned chromosomes. However, the link between SAC activation and chromosome alignment is poorly understood. Here we show that Mad1, a core SAC component, plays a hitherto concealed role in chromosome alignment. Protein-protein interaction screening revealed that fission yeast Mad1 binds the plus-end-directed kinesin-5 motor protein Cut7 (Eg5 homologue), which is generally thought to promote spindle bipolarity. We demonstrate that Mad1 recruits Cut7 to kinetochores of misaligned chromosomes and promotes chromosome gliding towards the spindle equator. Similarly, human Mad1 recruits another kinetochore motor CENP-E, revealing that Mad1 is the conserved dual-function protein acting in SAC activation and chromosome gliding. Our results suggest that the mitotic checkpoint has co-evolved with a mechanism to drive chromosome congression.
AB - For proper partitioning of genomes in mitosis, all chromosomes must be aligned at the spindle equator before the onset of anaphase. The spindle assembly checkpoint (SAC) monitors this process, generating a â € wait anaphase'signal at unattached kinetochores of misaligned chromosomes. However, the link between SAC activation and chromosome alignment is poorly understood. Here we show that Mad1, a core SAC component, plays a hitherto concealed role in chromosome alignment. Protein-protein interaction screening revealed that fission yeast Mad1 binds the plus-end-directed kinesin-5 motor protein Cut7 (Eg5 homologue), which is generally thought to promote spindle bipolarity. We demonstrate that Mad1 recruits Cut7 to kinetochores of misaligned chromosomes and promotes chromosome gliding towards the spindle equator. Similarly, human Mad1 recruits another kinetochore motor CENP-E, revealing that Mad1 is the conserved dual-function protein acting in SAC activation and chromosome gliding. Our results suggest that the mitotic checkpoint has co-evolved with a mechanism to drive chromosome congression.
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U2 - 10.1038/ncb3219
DO - 10.1038/ncb3219
M3 - Article
C2 - 26258632
AN - SCOPUS:84940597006
SN - 1465-7392
VL - 17
SP - 1124
EP - 1133
JO - Nature Cell Biology
JF - Nature Cell Biology
IS - 9
ER -