Rad21Scc1

RAD21Scc1, commonly referred to as RAD21 or Scc1, is the kleisin subunit of the cohesin complex in eukaryotic cells. It forms a ring together with the SMC1 and SMC3 ATPases and a STAG (SA1/SA2 in vertebrates) subunit, enabling sister chromatid cohesion from DNA replication through mitosis. The cohesin complex is loaded onto chromosomes by the Scc2-Scc4 loader complex, establishing cohesion during S phase and maintaining it until anaphase.

Mechanism and regulation: RAD21Scc1 bridges the Smc1 and Smc3 heads, closing the cohesin ring around sister chromatids. At anaphase, RAD21Scc1 is cleaved by separase (ESPL1), releasing the sister chromatids to allow separation. The activity of separase is tightly controlled by securin (PTTG1) and by various phosphorylation events and proteolytic processes that coordinate the timing of cohesion release with chromosome segregation. Post-translational modifications of RAD21Scc1 also influence its stability and function.

Biological roles: In addition to maintaining sister chromatid cohesion, cohesin and its RAD21Scc1 subunit participate in DNA repair by homologous recombination, regulation of gene expression, and three-dimensional genome organization. These roles contribute to genome stability and proper transcriptional programs during development and cell differentiation.

Clinical and evolutionary context: Aberrant regulation or mutation of RAD21Scc1 can lead to genomic instability and aneuploidy, processes associated with cancer and developmental disorders. RAD21Scc1 is conserved across diverse eukaryotes, with species-specific naming conventions (RAD21 in some organisms, Scc1 in others) but preserving core cohesin functions.