Abstract: The invention provides nucleic acid molecules, designated separase nucleic acid molecules, which encode separase, an endopeptidase that modulates sister chromatid separation. The invention also provides recombinant expression vectors containing separase nucleic acid molecules and host cells into which the expression vectors have been introduced. The invention still further provides separase proteins, fusion proteins, antigenic peptides and anti-separase antibodies. The invention also provides methods for the identification of modulators of separase, methods of modulating separase, methods of modulating sister chromatid separation, and methods for the treatment of disorders related to aberrant sister chromatid separation, such as cancer, Down's syndrome, and spontaneous fetal abortion.