Proper metaphase spindle length is determined by centromere proteins Mis12and Mis6 required for faithful chromosome segregation

High-fidelity chromosome transmission is fundamental in controlling the qua lity of the cell division cycle. The spindle pole-to-pole distance remains constant from metaphase to anaphase A. We show that fission yeast sister ce ntromere-connecting proteins, Mis6 and Mis12 are required for correct spind le morphogenesis, determining metaphase spindle length, Thirty-five to sixt y percent extension of metaphase spindle length takes place in mis6 and mis 12 mutants. This may be due to incorrect spindle morphogenesis containing i mpaired sister centromeres or force unbalance between pulling by the linked sister kinetochores and kinetochore-independent pushing. The mutant spindl e fully extends in anaphase, although it is accompanied by drastic missegre gation by aberrant sister centromere separation. Hence, metaphase spindle l ength may be crucial for segregation fidelity. Suppressors of mis12 partly restore normal metaphase spindle length. In mis4 that is defective in siste r chromatid cohesion, metaphase spindle length is also long, but anaphase s pindle extension is blocked, probably due to the activated spindle checkpoi nt, Extensive missegregation is caused in mis12 only when Mis12 is inactiva ted from the previous M through to the following M, an effective way to avo id missegregation in the cell cycle. Misle has conserved homologs in buddin g yeast and filamentous fungi.