Abstract
In eukaryotic cells, replicated DNA strands remain physically connected until their segregation to opposite poles of the cell during anaphase. This "sister chromatid cohesion" is essential for the alignment of chromosomes on the mitotic spindle during metaphase. Cohesion depends on the multisubunit cohesin complex, which possibly forms the physical bridges connecting sisters. Proteolytic cleavage of cohesin's Sccl subunit at the metaphase to anaphase transition is essential for sister chromatid separation and depends on a conserved protein called separin. We show here that separin is a cysteine protease related to caspases that alone can cleave Sccl in vitro. Cleavage of Sccl in metaphase arrested cells is sufficient to trigger the separation of sister chromatids and their segregation to opposite cell poles.
Publication types
-
Research Support, Non-U.S. Gov't
MeSH terms
-
Amino Acid Sequence
-
Amino Acid Substitution / genetics
-
Anaphase* / drug effects
-
Animals
-
Binding Sites
-
Cell Cycle Proteins / antagonists & inhibitors
-
Cell Cycle Proteins / chemistry
-
Cell Cycle Proteins / isolation & purification
-
Cell Cycle Proteins / metabolism*
-
Cell Line
-
Chromosomal Proteins, Non-Histone
-
Chromosome Segregation / drug effects
-
Chromosomes, Fungal / drug effects
-
Chromosomes, Fungal / metabolism
-
Conserved Sequence / genetics
-
Cysteine Endopeptidases / chemistry
-
Cysteine Endopeptidases / classification
-
Cysteine Endopeptidases / isolation & purification
-
Cysteine Endopeptidases / metabolism
-
Cysteine Proteinase Inhibitors / metabolism
-
Cysteine Proteinase Inhibitors / pharmacology
-
Endopeptidases / metabolism
-
Fungal Proteins / antagonists & inhibitors
-
Fungal Proteins / chemistry
-
Fungal Proteins / isolation & purification
-
Fungal Proteins / metabolism
-
Mitosis / drug effects
-
Molecular Sequence Data
-
Nuclear Proteins
-
Phosphoproteins
-
Phosphorylation
-
Protein Binding
-
Protein Processing, Post-Translational* / drug effects
-
Protein Structure, Tertiary
-
Recombinant Proteins / isolation & purification
-
Recombinant Proteins / metabolism
-
Saccharomyces cerevisiae Proteins
-
Separase
-
Sequence Alignment
-
Spodoptera
-
Yeasts / cytology*
-
Yeasts / drug effects
-
Yeasts / enzymology
-
Yeasts / metabolism*
Substances
-
Cell Cycle Proteins
-
Chromosomal Proteins, Non-Histone
-
Cysteine Proteinase Inhibitors
-
Fungal Proteins
-
MCD1 protein, S cerevisiae
-
Nuclear Proteins
-
Phosphoproteins
-
Recombinant Proteins
-
Saccharomyces cerevisiae Proteins
-
Endopeptidases
-
TEV protease
-
Cysteine Endopeptidases
-
Separase