No abstract

Kinesin motors provide the molecular forces at the kinetochore-microtubule interface and along the spindle to control chromosome segregation. During meiosis with two rounds of microtubule assembly-disassembly, the roles of motor proteins remain unexplored. We observed that in contrast to mitosis, Cin8 and Kip3 together are indispensable for meiosis. While examining meiosis in cin8Δ kip3Δ cells, we detected chromosome breakage in the meiosis II cells. The double mutant exhibits a delay in cohesin removal during anaphase I. Consequently, some cells fail to undergo meiosis II and form dyads, while some, as they progress through meiosis II, cause a defect in chromosome integrity. We believe that in the latter cells, an imbalance of spindle-mediated force and the simultaneous persistence of cohesin on chromosomes cause their breakage. We provide evidence that tension generated by Cin8 and Kip3 through microtubule cross-linking is essential for signaling efficient cohesin removal and the maintenance of chromosome integrity during meiosis.

During mitosis, the budding yeast, kinetochores remain attached to microtubules, except for a brief period during S phase. Sister-kinetochores separate into two clusters (bi-lobed’ organization) upon stable end-on attachment to microtubules emanating from opposite spindle poles. However, in meiosis, the outer kinetochore protein Ndc80 reassembles at the centromeres much later after prophase I, establishing new kinetochore-microtubule attachments. Perhaps due to this, despite homolog bi-orientation, we observed that the kinetochores (Ndc80) are linearly dispersed between spindle-poles during metaphase I of meiosis. The presence of end-on attachment marker Dam1 as a cluster near each pole suggests one of the other possibilities that the pole-proximal and pole-distal kinetochores are attached end-on and laterally to the microtubules, respectively. Colocalization studies of kinetochores and kinesin motors suggest that budding yeast kinesin 5, Cin8 and Kip1 perhaps localize to the end-on attached kinetochores while kinesin 8, Kip3 resides at all the kinetochores. Our findings, including kinesin 5 and Ndc80 co-appearance after prophase I and reduced Ndc80 levels in cin8 null mutant, suggest that kinesin motors are crucial for kinetochore reassembly and stability during early meiosis. Thus, this work reports yet another meiosis specific function of kinesin motors.

Kinesin motors provide the molecular forces at the kinetochore-microtubule interface and along the spindle to control chromosome segregation. During meiosis with the two rounds of microtubule assembly-disassembly, the roles of motor proteins remain unexplored. We observed that in contrast to mitosis Cin8 (kinesin 5) and Kip3 (kinesin 8) together are indispensable in meiosis. Examining the meiosis in cin8∆ kip3∆ cells, we detected chromosome breakage in the meiosis II cells. The double mutant exhibits delay in the cohesin removal and spindle elongation during anaphase I. Consequently, some cells abrogate meiosis II and form dyads while some, as they progress through meiosis II, cause defect in chromosome integrity. We believe that in the latter cells, an imbalance of spindle mediated force and simultaneous persistent cohesin on the chromosomes cause their breakage. We provide evidence that tension generated by Cin8 and Kip3 through microtubule cross-linking is essential for signaling efficient cohesin removal and maintenance of chromosome integrity during meiosis.SummaryMolecular motors generate forces that facilitate chromosome segregation. Unlike mitosis, in meiosis, two times chromosome segregation occur with twice microtubule assembly/disassembly. This work reports that the motor mediated forces are crucial for cohesin removal in meiosis and thus maintain genome integrity.