#cohesin

Cell Division

Which enzyme is responsible for breaking down cohesin to allow sister chromatid separation?

Sister chromatid cohesion mediated by cohesin ring complex with SMC1 and SMC3 coiled-coil proteins forming V-shaped dimer bridged by kleisin Rad21 that closes tripartite ring embracing both sister DNAs from replication until anaphase. Opening requires proteolytic cleavage rather than dissociation. Separase, large 230 kDa cysteine endopeptidase belonging to CD clan with catalytic histidine-cysteine dyad analogous to caspases, serves as cleaving enzyme. Before anaphase, separase kept inactive through two layers: binding of securin pseudosubstrate occupying active site, and cyclin B-CDK1 mediated

Ref: Uhlmann et al., Nature 2000, Mechanism of Separase. Nasmyth, Science 2002, Cohesin Cleavage.

View Details

Cell Cycle Regulation

Which enzyme cleaves cohesin at anaphase onset?

Persistent cohesion between sister chromatids depends on cohesin, tetrameric ring of Smc1, Smc3 ATPases, kleisin Scc1/Rad21 and stromalin SA1/2 subunits embracing replicated DNA strands. During prophase most arm cohesin dissociates via Wapl-dependent opening after Plk1 and Aurora B phosphorylation of SA2, while centromeric pool protected by Shugoshin recruiting PP2A-B56 counteracting phosphorylation remains for biorientation. Final dissolution at anaphase onset requires proteolytic cleavage. Separase, 230 kDa cysteine protease of CD clan, executes this. Kept inactive by dual mechanisms includi

Ref: Nasmyth & Haering, Cohesin and Separase Regulation, Annu Rev Genet 2009; Uhlmann, Separase in Anaphase and Beyond.

View Details

Nucleosome Packing

SMC proteins are involved in:

Structural Maintenance of Chromosomes proteins represent large ATPase machines forming elongated coiled-coil dimers with hinge domain closing ring-like structures embracing DNA duplexes. Condensin complexes SMC2/SMC4 compact mitotic chromosomes via loop extrusion, cohesin SMC1/SMC3 holds sister chromatids together from S phase until anaphase cleavage by separase, SMC5/SMC6 aids homologous recombination repair at collapsed forks. Mutations produce chromosome missegregation, aneuploidy and repair defects. Proteins localize to scaffold attachment regions and utilize ATP hydrolysis to extrude loop

Ref: Hirano T 2016 Nat Rev Mol Cell Biol SMC; Lodish et al., Chapter 19: SMC Proteins Chromosome Maintenance

View Details

Nucleosome Packing

Major scaffold protein involved in loop formation is:

Chromosome condensation during prophase requires scaffold proteins shaping 30 nanometer fiber loops into cylindrical chromatids 700 nanometers wide. Topoisomerase II alpha, type II enzyme cleaving both DNA strands, passing duplex through break and resealing, resolves sister chromatid catenations, adjusts supercoiling and forms axial scaffold along chromatid center overlapping condensin complex. Immunofluorescence shows topoisomerase II colocalizes with condensin along axis. DNA polymerase synthesizes DNA, RNA polymerase transcribes, ligase joins Okazaki fragments, but scaffold architecture and

Ref: Earnshaw and Laemmli 1983 Scaffold; Alberts et al., Molecular Biology of the Cell, Chapter 19: Scaffold Protein Topoisomerase II

View Details