title: Mad1 promotes chromosome congression by anchoring a kinesin motor to the kinetochore.
abstract: 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.
authors.affiliation: Laboratory of Chromosome Dynamics, Institute of Molecular and Cellular Biosciences, University of Tokyo, Yayoi, Tokyo 113-0032, Japan.|Graduate Program in Biophysics and Biochemistry, Graduate School of Science, University of Tokyo, Yayoi, Tokyo 113-0032, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Akera
authors.affiliation: Laboratory of Chromosome Dynamics, Institute of Molecular and Cellular Biosciences, University of Tokyo, Yayoi, Tokyo 113-0032, Japan.|Graduate Program in Biophysics and Biochemistry, Graduate School of Science, University of Tokyo, Yayoi, Tokyo 113-0032, Japan.
authors.forename: Yuhei
authors.initials: Y
authors.lastname: Goto
authors.affiliation: Graduate Program in Biophysics and Biochemistry, Graduate School of Science, University of Tokyo, Yayoi, Tokyo 113-0032, Japan.
authors.forename: Masamitsu
authors.initials: M
authors.lastname: Sato
authors.affiliation: Graduate Program in Biophysics and Biochemistry, Graduate School of Science, University of Tokyo, Yayoi, Tokyo 113-0032, Japan.
authors.forename: Masayuki
authors.initials: M
authors.lastname: Yamamoto
authors.affiliation: Laboratory of Chromosome Dynamics, Institute of Molecular and Cellular Biosciences, University of Tokyo, Yayoi, Tokyo 113-0032, Japan.|Graduate Program in Biophysics and Biochemistry, Graduate School of Science, University of Tokyo, Yayoi, Tokyo 113-0032, Japan.
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Watanabe
mesh_terms: D000595:Amino Acid Sequence; D018797:Cell Cycle Proteins / Q000502:physiology*; D020090:Chromosome Segregation; D015825:Chromosomes, Fungal / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D016547:Kinesins / Q000378:metabolism; D018386:Kinetochores / Q000378:metabolism*; D059566:M Phase Cell Cycle Checkpoints; D008938:Mitosis; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000502:physiology*; D011485:Protein Binding; D021381:Protein Transport; D012568:Schizosaccharomyces / Q000235:genetics / Q000378:metabolism*; D029702:Schizosaccharomyces pombe Proteins / Q000378:metabolism / Q000502:physiology*
chemical_list: D018797:Cell Cycle Proteins; C104159:Cut7 protein, S pombe; D009687:Nuclear Proteins; D029702:Schizosaccharomyces pombe Proteins; C501383:mad1 protein, S pombe; D016547:Kinesins