Cohesinkomplexet

Cohesinkomplexet, commonly referred to in English as the cohesin complex, is a conserved multiprotein complex essential for sister chromatid cohesion after DNA replication and until anaphase, thereby ensuring accurate chromosome segregation during cell division. Beyond its core role in cohesion, cohesin participates in organizing chromatin architecture, DNA repair, and regulation of gene expression by shaping the three-dimensional genome.

The core human complex consists of SMC1A, SMC3, RAD21 (also known as SCC1), and one of the SA subunits, STAG1 or STAG2. The Smc1/Smc3 proteins form a ring-like structure with RAD21 bridging them, and STAG1/2 stabilizes the assembly. Additional regulatory factors modulate loading, stabilization, and release: loading is driven by the NIPBL/Mau2 complex; acetylation of SMC3 by ESCO1/ESCO2 stabilizes cohesion during S phase; WAPL and PDS5 promote release, while Sororin helps protect cohesion in certain contexts.

Cohesin also contributes to genome organization by promoting the formation of chromatin loops and topologically associating domains, influencing transcription and replication timing. Its activity is tightly regulated throughout the cell cycle, with distinct loading, establishment, and release phases. Defects in cohesin components or regulators are associated with developmental disorders, most notably Cornelia de Lange syndrome, and have been observed in various cancers. The cohesin pathway is evolutionarily conserved from yeast to humans, reflecting its fundamental role in maintaining genome integrity and regulating genome architecture.