Rad21 is one of the major cohesin subunits that holds sister chromatids together until anaphase, when proteolytic cleavage by separase, a caspaselike enzyme, allows chromosomal separation. Rad21 interacts with Rec8 to form a cohesin complex that functions in sister chromatid alignment. Rad21 is also involved in the repair of double-strand breaks in DNA and is essential for mitotic growth. Rad21 undergoes a C-terminal cleavage induced by diverse stimuli right before apoptosis. The cleavage product migrates to the cytoplasm and is involved in early events in the apoptotic pathway and it amplifiies the cell death signal in a positive-feedback manner.