RAD21

RAD21 is a gene that encodes a core component of the cohesin complex, a conserved multisubunit protein complex essential for sister chromatid cohesion from DNA replication through cell division. In humans, RAD21 is the cohesin subunit often referred to as SCC1 in other species and corresponds to a protein of about 631 amino acids localized to the nucleus.

Within the cohesin ring, RAD21 serves as a bridge connecting the structural maintenance of chromosomes proteins SMC1A and SMC3, while the non-SMC subunits SA1 (STAG1) or SA2 (STAG2) regulate the complex. The ring encircles sister chromatids to maintain their cohesion; when cells enter anaphase, the protease separase cleaves RAD21, allowing sister chromatids to separate and chromosomes to segregate.

In addition to its role in cohesion, cohesin participates in DNA double-strand break repair, replication fork stability, and the regulation of transcription and higher-order chromatin structure, influencing gene expression programs across the genome. RAD21 function is coordinated with other regulators such as PDS5 proteins and WAPL.

RAD21 is primarily nuclear and its activity is tightly controlled during the cell cycle. Disruption of RAD21 function or expression can lead to genomic instability and altered transcriptional regulation. In organisms, RAD21 is essential for development, and in humans somatic alterations, including copy number changes and mutations in RAD21 or other cohesin components, have been observed in various cancers and developmental disorders, reflecting the protein’s crucial role in genome maintenance.