Centromeric Cohesin: Molecular Glue and Much More

Abstract

Sister chromatid cohesion, mediated by the cohesin complex, is a prerequisite for faithful chromosome segregation during mitosis. Premature release of sister chromatid cohesion leads to random segregation of the genetic material and consequent aneuploidy. Multiple regulatory mechanisms ensure proper timing for cohesion establishment, concomitant with DNA replication, and cohesion release during the subsequent mitosis. Here we summarize the most important phases of the cohesin cycle and the coordination of cohesion release with the progression through mitosis. We further discuss recent evidence that has revealed additional functions for centromeric localization of cohesin in the fidelity of mitosis in metazoans. Beyond its well-established role as "molecular glue", centromeric cohesin complexes are now emerging as a scaffold for multiple fundamental processes during mitosis, including the formation of correct chromosome and kinetochore architecture, force balance with the mitotic spindle, and the association with key molecules that regulate mitotic fidelity, particularly at the chromosomal inner centromere. Centromeric chromatin may be thus seen as a dynamic place where cohesin ensures mitotic fidelity by multiple means.