@article{Taxol-Stabilized:1567,
      recid = {1567},
      author = {Proudfoot, Kathleen Grant},
      title = {Taxol-Stabilized Yeast Microtubules Reveal that a Subset  of Spindle Checkpoint Proteins Delay Anaphase Onset in  Response to Low Tension},
      publisher = {The University of Chicago},
      school = {Ph.D.},
      address = {2017-12},
      pages = {158},
      abstract = {To ensure genome stability during mitosis, the mitotic  spindle must segregate sister chromosomes accurately.  Multiple surveillance mechanisms, collectively referred to  as the mitotic checkpoint, function to delay anaphase onset  if sister chromosomes are not bound to microtubules from  opposite spindle poles.  Dominant signaling pathways within  the mitotic checkpoint are the Spindle Assembly Checkpoint  (SAC), which delays anaphase when kinetochores are not  stably attached to microtubules, and the error correction  mechanism, which induces detachment when  microtubule-kinetochore attachments are not under tension.   Together, these mechanisms promote stable, bipolar  attachments in which dynamic microtubules can generate  tension across sister kinetochores.  However, the  interdependency of kinetochore-microtubule attachment and  tension has proved challenging to understanding whether  this model fully explains how the mitotic checkpoint  responds to the tension status at kinetochores. Unlike  higher eukaryotes, budding yeast kinetochores bind only one  microtubule, simplifying the relationship between  attachment and tension. To address the role of tension in  the mitotic checkpoint, we developed a Taxol-sensitive  yeast model to reduce tension by stabilizing microtubules  in fully assembled spindles. Our results show that reducing  tension on bipolar, attached kinetochores delays anaphase  onset. The tension-mediated delay is transient relative to  the SAC delay imposed by unattached kinetochores.  Furthermore, it requires the SAC proteins Bub1 and Bub3,  but persists without Mad1, Mad2 and Mad3 (yeast BubR1).  Together, our results demonstrate that reduced tension  generates a ‘wait-anaphase’ signal during the mitotic  checkpoint that is temporally and mechanistically distinct  from that of unattached kinetochores.},
      url = {http://knowledge.uchicago.edu/record/1567},
      doi = {https://doi.org/10.6082/uchicago.1567},
}