CohesinKomplex

The Cohesin Complex, known in German-language literature as the CohesinKomplex, is a highly conserved multi-subunit protein complex essential for sister chromatid cohesion, chromatin organization, and DNA repair. It forms a ring-like structure that can encircle two sister chromatids, thereby holding them together from DNA replication in S phase until their separation in mitosis. Beyond cohesion, cohesin also contributes to higher-order chromosome architecture and regulation of gene expression.

The core subunits are two structural maintenance of chromosome (SMC) proteins, SMC1 and SMC3, which form a V-shaped heterodimer. A kleisin subunit, RAD21 (also called SCC1 in some species), closes the ring by linking the Smc heads. Additional non-SMC subunits, STAG1 or STAG2 (also known as SA1 and SA2), stabilize the complex and modulate its activity. The complex is loaded onto chromatin by the loader complex composed of NIPBL (Scc2) and MAU2 (Scc4); regulation of loading and unloading involves proteins such as WAPL and PDS5A/B.

Loading and establishment of cohesion occur mainly during the cell cycle's S phase. The ring is loaded onto DNA by the NIPBL-MAU2 loader, and the sister chromatids are held together through acetylation of SMC3 by ESCO1/ESCO2, which stabilizes cohesion. Cohesin is removed in a regulated manner as cells progress through mitosis: prophase–prometaphase-associated release involves WAPL, while the onset of anaphase triggers cleavage of RAD21 by separase to linearize the ring and allow sister chromatid separation.

Functions extend beyond cohesion to the organization of chromatin loops and topologically associating domains, guidance of DNA repair by homologous recombination, and influence on transcriptional regulation.

Dysfunction of cohesin components or regulators is linked to human disorders, including Cornelia de Lange syndrome, and to various cancers, reflecting the complex’s essential role in genome integrity and gene regulation. The cohesin complex is conserved from yeast to humans and remains a focus of research on chromosome biology and genome organization.