Separase is a cystein protease that triggers chromosome segregation at anaphase onset by cleaving cohesin, a
complex that links replicated chromatids. Separase is inhibited by securin, which is degraded at the metaphase-
anaphase transition. Although the machinery for dissolving sister chromatids cohesion is conserved from yeast to
human, the regulation of this process appears to be more complex in higher eukaryotes than in yeast. In vertebrates,
additional regulatory mechanisms of the separase have been reported using in vitro studies. Separase undergoes
autocatalytic cleavage once the securin has been destroyed and once inhibitory phosphates have been removed
from separase. If separase dephosphorylation and autocatalytic cleavage are essential for separase regulation in
vivo is unknown. Here we propose to investigate separase regulation in mice using bacterialartificial chromosome
mediated transgenesis.