Eykelenboom, J. K.; Gierlinski, M.; Yue, Z.; Tanaka, T. U.

During early mitosis, chromosomes are reorganized from their relatively decompacted interphase state into characteristic mitotic rod-shaped structures. This process is important to allow correct segregation of newly replicated sister chromatids to the opposite spindle poles during anaphase. The mitotic chromosome reorganization is controlled by two protein complexes named condensin I and condensin II. Condensin II is particularly important for achieving sister chromatid separation (resolution) whilst condensin I is required for chromosome condensation (compaction). Although sister chromatid resolution occurs 15-20 min earlier before chromosome compaction, it is not yet clear how these events are temporally coordinated or whether this temporal coordination is important to ensure chromosome segregation later in mitosis. One hypothesis is that the temporal coordination is achieved through different subcellular localisation of two condensin complexes; whilst condensin II localizes in the nucleus, condensin I is restricted to the cytoplasm, during interphase and prophase. In this study we tested this hypothesis by engineering the localization of condensin I to the nucleus. We monitored sister chromatid resolution and chromosome compaction by real-time imaging that visualized selected neighboring chromosome loci. We found that localization of condensin I to the nucleus led to precocious chromosome compaction during prophase with a similar timing to sister chromatid resolution. We also monitored later stages of mitosis and found that cells expressing nuclear condensin I subsequently exhibited frequent chromosome mis-segregation in anaphase. Therein, the majority of mis-segregated chromosomes consisted of lagging chromosomes involving both sister chromatids. This suggests that the temporal control of mitotic chromosome reorganization is crucial for high-fidelity chromosome segregation. In conclusion, the exclusion of condensin I from the nucleus during prophase delays chromosome compaction and allows condensin II to complete sister chromatid resolution, which ensures correct chromosome segregation later in mitosis.