Mad1 promotes chromosome congression by anchoring a kinesin motor to the kinetochore.

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 '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.

Citation

Takashi Akera, Yuhei Goto, Masamitsu Sato, Masayuki Yamamoto, Yoshinori Watanabe. Mad1 promotes chromosome congression by anchoring a kinesin motor to the kinetochore. Nature cell biology. 2015 Sep;17(9):1124-33

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PMID: 26258632

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