Degradation of Drosophila PIM regulates sister chromatid separation duringmitosis

Drosophila Pimples (PIM) and Three rows (THR) are required for sister chrom atid separation in mitosis. PIM accumulates during interphase and is degrad ed rapidly during mitosis. This degradation is dependent on a destruction b ox similar to that of B-type cyclins. Nondegradable PIM with a mutant destr uction box call rescue sister chromatid separation in pim mutants but only when expressed at low levels. Higher levels of nondegradable PIM, as well a s overexpression of wild-type PIM, inhibit sister chromatid separation. Mor eover, cells arrested in mitosis before sister chromatid separation (by col cemid or by mutations in fizzy/CDC20) fail to degrade PIM. Thus, although n ot related by primary sequence, PIM has intriguing functional similarities to the securin proteins of budding yeast, fission yeast, and vertebrates. W hereas these securins are known to form a complex with separins, we show th at PIM associates in vivo with THR, which does not contain the conserved se parin domain.