Modeling the spatial organization of replicated chromosomes in yeast reveals a loose asymmetric cohesion between sister chromatids.

Following DNA replication, cohesion maintains sister chromatids (SCs) in spatial proximity with a certain degree of alignment. This tethering, mediated by the cohesin complex, may facilitate DNA repair and enable proper chromosome individualization and segregation during mitosis. However, it is still unclear how cohesion is established and how it reshapes the relative organization of replicated chromosomes to achieve its functions. In this study, we address these questions in the biological context of budding yeast by disentangling the interplay between two major structural functions of cohesin: organizing individual chromatids through loop extrusion and SCs through cohesion. Combining polymer modeling and detailed analysis of recent experimental data of replicated chromosomes in G2/M, we show that extruding and cohesive cohesins are sparsely distributed, leading to mildly compacted and loosely aligned SCs. Genome-wide analysis of inter-chromatid contact maps in wild-type and mutant conditions suggests that cohesion is asymmetric, favoring the tethering between non-homologous cohesin-enriched regions. Our work highlights the dual role played by cohesin in structuring the replicated genome and questions the functions of cohesion in the context of asymmetric, partial alignment of SCs.