cohesinkomplekset

Cohesin complex, also known as the cohesin complex, is a conserved multi-subunit protein complex that mediates sister chromatid cohesion, aids in DNA repair, and contributes to three-dimensional genome organization. The core ring is formed by Smc1 (SMC1A in humans) and Smc3, two long coiled-coil proteins with ATPase heads, together with the kleisin subunit RAD21 (Scc1), which closes the ring by bridging the two head domains. A STAG subunit (SA1/SA2; STAG1/STAG2) associates with RAD21 and stabilizes the complex, giving variants such as cohesin-SA1 and cohesin-SA2.

Assembly and regulation: Cohesin is loaded onto chromosomes by the Scc2–Scc4 loader complex (NIPBL–MAU2 in humans). Establishment of cohesion during S phase requires acetylation of Smc3 by ESCO1/ESCO2, which stabilizes the ring on sister chromatids and counteracts release factors. Release is mediated by WAPL and PDS5; during mitosis, a prophase pathway removes cohesin from chromosome arms, while centromeric cohesion is protected until anaphase when separase cleaves RAD21 to trigger sister chromatid separation.

Functions: In addition to maintaining cohesion, cohesin promotes DNA repair by homologous recombination by holding sister templates together; it shapes higher-order chromatin architecture and participates in gene regulation and the formation of chromatin loops and topologically associating domains (TADs).

Clinical relevance: Mutations in cohesin subunits or regulators cause developmental disorders such as Cornelia de Lange syndrome and are frequently found in cancers (notably STAG2 mutations). The complex is thus important for development, genome stability, and healthy cellular function.