Spatial Regulation of Kinetochore Microtubule Attachments by Destabilization at Spindle Poles in Meiosis I

Abstract

To ensure accurate chromosome segregation in cell division, erroneous kinetochore-microtubule (MT) attachments are recognized and destabilized . Improper attachments typically lack tension between kinetochores and are positioned off-center on the spindle. Low tension is a widely accepted mechanism for recognizing errors , but whether chromosome position regulates MT attachments has been difficult to test. We exploited a meiotic system in which kinetochores attached to opposite spindle poles differ in their interactions with MTs and therefore position and tension can be uncoupled. In this system, homologous chromosomes are positioned off-center on the spindle in oocytes in meiosis I, while under normal tension, as a result of crossing mouse strains with different centromere strengths, manifested by unequal kinetochore protein levels. We show that proximity to spindle poles destabilizes kinetochore-MTs and that stable attachments are restored by inhibition of Aurora A kinase at spindle poles. During the correction of attachment errors, kinetochore-MTs detach near spindle poles to allow formation of correct attachments. We propose that chromosome position on the spindle provides spatial cues for the fidelity of cell division.