Rules of engagement for condensins and cohesins guide mitotic chromosome formation

Samejima, K., Gibcus, J.H., Abraham, S., Cisneros-Soberanis, F., Samejima, I., Beckett, A.J., Pučeková, N., Alba Abad, M., Spanos, C., Medina-Pritchard, B., Paulson, J.R., Xie, L., Jeyaprakash, A.A., Prior, I.A., Mirny, L.A., Dekker, J., Goloborodko, A., and Earnshaw, W.C. 

By Jenna Hare, Bird Lab

During mitosis, chromosomes must transition from their uncondensed, interphase state to a highly compacted, rod-shaped structure. This compaction, which begins during prophase, is essential for organising DNA into manageable, stable units that can be precisely segregated during anaphase. The transformation is driven by structural maintenance of chromosomes (SMC) complexes, which act as molecular ‘motors’ that reorganise chromatin through loop extrusion whilst maintaining sister chromatid cohesion. There are four key SMC complexes involved: condensin I, condensin II, extrusive cohesin, and cohesive cohesin. During early prophase, chromatin is organised into cohesin-dominated domains, such as topologically associating domains (TADs), which are important for interphase gene regulation. In late prophase, this structure is replaced by a condensin-dominated loop array, which compacts chromatin lengthwise into a helical, "bottlebrush-like" scaffold. The timing of this transition suggests frequent interactions between condensin and cohesin, yet the rules of these encounters have remained unclear.

In this study, researchers in the Earnshaw Lab and their collaborators in the Dekker, Mirny and Goloborodko labs combined cell biology, imaging, proteomics, Hi-C, and polymer modelling to dissect the roles and interactions of SMC complexes during mitosis. By selectively depleting different combinations of SMCs in synchronized chicken cells, they uncovered a set of three key "rules of engagement" that control SMC behaviour on chromatin:

1. Condensin evicts extrusive cohesin, which erases interphase chromatin organization to enable compaction.
2. Condensin bypasses cohesive cohesin, allowing continued loop extrusion while maintaining cohesion of sister chromatids.
3. Condensins stall upon encountering one another, generating arrays of consecutive, non-overlapping loops that form the compact chromosome state.

Samejima et al., also measured loop extrusion rates in vivo, finding that condensins extrude loops at 1–3 kilobases per second. Moreover, condensin II initiates the formation of larger loops early in prophase, while condensin I, which gains access after nuclear envelope breakdown, adds smaller, nested loops. These findings broaden our understanding of mitotic chromosomes and demonstrate how localised SMC activity changes chromosome structure. This work provides a foundation for exploring how disruptions to SMC regulation might contribute to diseases such as cancer and cohesinopathies.