Nuclear exclusion of condensin I in prophase coordinates mitotic chromosome reorganization to ensure complete sister chromatid resolution.

Abstract

During early mitosis, chromosomes transition from their unfolded interphase state to the distinct rod-shaped structures characteristic of mitosis. This process allows correct segregation of replicated sister chromatids to the opposite spindle poles during anaphase. Two protein complexes, named condensin I and condensin II, facilitate mitotic chromosome organization. Condensin II is important for achieving sister chromatid separation (resolution), while condensin I is required for chromosome condensation (folding). Although sister chromatid resolution occurs earlier than chromosome folding, it is not yet clear how these events are coordinated through time or whether this is important for correct chromosome segregation. In this study, we tested the hypothesis that temporal control is achieved through differential localization of the two condensin complexes; i.e., while condensin II localizes in the nucleus, condensin I is excluded from the nucleus in interphase and prophase. We engineered the localization of condensin I to the nucleus and monitored sister chromatid resolution and chromosome folding by real-time imaging. We found that localization of condensin I to the nucleus led to precocious chromosome folding during prophase, with similar timing to sister chromatid resolution. Furthermore, this change led to incomplete sister chromatid resolution in prometaphase/metaphase and frequent chromosome missegregation in anaphase, in which most missegregated chromosomes consisted of lagging chromosomes involving both sister chromatids. We conclude that, in a physiological context, the exclusion of condensin I from the nucleus during prophase delays chromosome folding and allows condensin II to complete sister chromatid resolution, which ensures correct chromosome segregation later in mitosis.