Loss of cohesion between sister chromatids triggers their segregation durin
g anaphase. Recent work has identified both a cohesin complex that holds si
sters together and a sister-separating protein, separin, that destroys cohe
sion. Separins are bound by inhibitory proteins whose proteolysis at the me
taphase-anaphase transition is mediated by the anaphase-promoting complex a
nd its activator protein CDC20 (APC(CDC20)). When chromosomes are misaligne
d, a surveillance mechanism (checkpoint) blocks sister separation by inhibi
ting APC(CDC20). Defects in this apparatus are implicated in causing aneupl
oidy in human cells.