New insights into mitotic chromosome condensation: a role for the prolyl isomerase Pin1.

Topoisomerase (Topo) IIalpha and condensin are essential for formation of mitotic chromosomes. However, the mechanism by which these two major components assemble during the chromosome condensation process had been unclear. Recent studies have revealed a coordinated and cooperative process, by which TopoIIalpha functions early to form an axis scaffold, whereas condensin complexes assemble at a later stage critical for chromosome integrity and subsequent segregation. Extending these observations, we recently found that the phosphorylation-dependent prolyl isomerase Pin1 is directly linked to the process. This conclusion is based on the observation of strong and extensive interactions of Pin1 with chromatin specifically at G2/M phase. Pin1 modulates the mitotic phosphorylation of TopoIIalpha by cdc2/cyclinB and promotes the association of phosphorylated TopoIIalpha with DNA elements to form an axis scaffold complex. The evidence highlights a critical role of Pin1 via its regulation of mitotic phosphorylation of key components in the chromosome condensation process.