Separase: a universal trigger for sister chromatid disjunction but not chromosome cycle progression.

J Cell Biol 2006 Mar;172(6):847-60

Research Institute of Molecular Pathology, A-1030 Vienna, Austria.

Separase is a protease whose liberation from its inhibitory chaperone Securin triggers sister chromatid disjunction at anaphase onset in yeast by cleaving cohesin's kleisin subunit. We have created conditional knockout alleles of the mouse Separase and Securin genes. Deletion of both copies of Separase but not Securin causes embryonic lethality. Loss of Securin reduces Separase activity because deletion of just one copy of the Separase gene is lethal to embryos lacking Securin. In embryonic fibroblasts, Separase depletion blocks sister chromatid separation but does not prevent other aspects of mitosis, cytokinesis, or chromosome replication. Thus, fibroblasts lacking Separase become highly polyploid. Hepatocytes stimulated to proliferate in vivo by hepatectomy also become unusually large and polyploid in the absence of Separase but are able to regenerate functional livers. Separase depletion in bone marrow causes aplasia and the presumed death of hematopoietic cells other than erythrocytes. Destruction of sister chromatid cohesion by Separase may be a universal feature of mitosis in eukaryotic cells.

Download full-text PDF

Source
http://dx.doi.org/10.1083/jcb.200506119DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2063729PMC
March 2006

Publication Analysis

Top Keywords

sister chromatid
16
separase
11
chromatid disjunction
8
separase securin
8
securin embryonic
8
separase universal
8
separase depletion
8
securin
5
chromatid separation
4
blocks sister
4
prevent aspects
4
separation prevent
4
cytokinesis chromosome
4
fibroblasts lacking
4
lacking separase
4
separase highly
4
replication fibroblasts
4
chromosome replication
4
mitosis cytokinesis
4
depletion blocks
4

Similar Publications