ARF6 protects sister chromatid cohesion to ensure the formation of stable kinetochore-microtubule attachments.

Abstract

Sister chromatid cohesion, facilitated by the cohesin protein complex, is crucial for the establishment of stable bipolar attachments of chromosomes to the spindle microtubules and their faithful segregation. Here, we demonstrate that the GTPase ARF6 prevents the premature loss of sister chromatid cohesion. During mitosis, ARF6-depleted cells normally completed chromosome congression. However, at the metaphase plate, chromosomes failed to establish stable kinetochore-microtubule attachments because of the impaired cohesion at centromeres. As a result, the spindle assembly checkpoint (SAC) was active and cyclin B ubiquitylation and degradation were blocked. Chromosomes and/or chromatids in these cells scattered gradually from the metaphase plate to the two poles of the cell or remained blocked at the metaphase plate for hours. Our study demonstrates that the small GTP-binding protein ARF6 is essential for maintaining centromeric cohesion between sister chromatids, which is necessary for the establishment of stable k-fibres, SAC satisfaction and the onset of anaphase.