Abstract

A Multi-Step Pathway for the Establishment of Sister Chromatid Cohesion

Highlights

  • Proper transmission of eukaryotic chromosomes during cell division requires DNA replication and three other DNAdependent processes: recombination-dependent DNA repair, sister chromatid cohesion, and chromosome condensation

  • To gain insight into the structure and function of structural maintenance of chromosomes (Smc) subunits, we developed a novel strategy of mutagenesis called random insertion dominant negative (RID), which generates informative alleles with high efficiency and should provide an effective tool to study any multi-subunit complex

  • The cohesin complex tethers together newly replicated chromosomes. The analyses of these RID mutants suggest that the tethering activity of cohesin is generated by two sequential chromatin-binding events, which are regulated both spatially and temporally

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Summary

Introduction

Proper transmission of eukaryotic chromosomes during cell division requires DNA replication and three other DNAdependent processes: recombination-dependent DNA repair, sister chromatid cohesion, and chromosome condensation. Each of these diverse processes requires protein complexes containing two members of the highly conserved structural maintenance of chromosomes (Smc) family of proteins [1,2,3]. Smc monomers fold in half at the Hinge domain, allowing the two a-helices to form a long antiparallel coiled-coil domain [6]. This folding juxtaposes the N- and C-terminal globular domains and the Walker A and B motifs, creating an Smc head domain with ATPase activity. Folded Smc monomers resemble a flexible dumbbell, with the Hinge and head domains separated by ;40 nm of coiled coil [6,7]

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