Cohesinien

Cohesinien are multisubunit protein complexes essential for sister chromatid cohesion, DNA repair, transcriptional regulation, and higher-order genome organization. They form a ring-like structure that encircles sister chromatids after DNA replication, helping hold them together until separation in anaphase.

Composition: The core cohesin ring comprises Smc1 and Smc3, which form an elongated V-shaped heterodimer, connected by the kleisin subunit Rad21 (also known as Scc1 in some organisms). A regulatory subunit, Scc3/SA1/SA2, stabilizes the complex and mediates interactions with other factors. In meiosis, Rec8 replaces Rad21.

Assembly and regulation: Cohesin is loaded onto chromatin by the Scc2/Scc4 loader complex. In S phase, Eco1/CTF7 acetylates Smc3, stabilizing cohesion. During prophase, Wapl promotes release of arm cohesin, while centromeric cohesion is protected by Shugoshin-PP2A until anaphase, when separase cleaves the kleisin subunit to release cohesin.

Roles: Beyond cohesion, cohesinien participate in DNA repair via homologous recombination, regulate gene expression, and contribute to 3D genome architecture by looping and organizing chromatin into topologically associating domains (TADs).

Clinical and evolutionary context: Mutations affecting cohesin components or regulators underlie cohesinopathies such as Cornelia de Lange syndrome; mutations in STAG2 and other cohesin members are found in various cancers. The complex is highly conserved across eukaryotes, with meiosis-specific variants like Rec8.