Cohesin

Cohesin is a multi-subunit protein complex essential for sister chromatid cohesion, DNA repair, and genome organization. In vertebrates, the core complex consists of the ATPases SMC1A and SMC3, a kleisin subunit (RAD21 in mitosis; REC8 in meiosis), and a STAG subunit (STAG1 or STAG2), along with additional SA proteins. The complex forms a ring-shaped structure that is thought to encircle sister chromatids to keep them together from DNA replication until anaphase.

Cohesin functions throughout the cell cycle to maintain sister chromatid cohesion, facilitate proper chromosome segregation, and contribute to DNA repair by homologous recombination. It also participates in shaping the three-dimensional organization of the genome, promoting chromatin loops and influencing transcriptional regulation.

Mechanistically, cohesin is loaded onto chromatin by the loading complex NIPBL-MAU2 (Scc2-Scc4 in yeast). In S phase, cohesion between sister chromatids is established, aided by acetylation of SMC3 by ESCO1/ESCO2 and stabilization by sororin in vertebrates. During mitosis, cohesin maintains cohesion until anaphase, when separase cleaves the kleisin subunit (RAD21), freeing the sister chromatids. Cohesin release is modulated by factors such as WAPL and PDS5. In meiosis, the meiosis-specific kleisin REC8 substitutes for RAD21, enabling stepwise separation of homologs and chromatids.

Clinical relevance includes cohesinopathies such as Cornelia de Lange syndrome, arising from mutations in cohesin components or regulators, and associations with various cancers, reflecting the importance of cohesin in development, genome stability, and gene expression.