The Structure and Function of SMC and Kleisin Complexes

Abstract

Protein complexes consisting of structural maintenance of chromosomes (SMC) and kleisin subunits are crucial for the faithful segregation of chromosomes during cell proliferation in prokaryotes and eukaryotes. Two of the best-studied SMC complexes are cohesin and condensin. Cohesin is required to hold sister chromatids together, which allows their bio-orientation on the mitotic spindle. Cleavage of cohesin's kleisin subunit by the separase protease then triggers the movement of sister chromatids into opposite halves of the cell during anaphase. Condensin is required to organize mitotic chromosomes into coherent structures that prevent them from getting tangled up during segregation. Here we describe the discovery of SMC complexes and discuss recent advances in determining how members of this ancient protein family may function at a mechanistic level.

Association of cohesin and Nipped-B with transcriptionally active regions of the Drosophila melanogaster genome

“…It contains four subunits, Smc1, Smc3, Rad21, and Stromalin (SA), which form a ring-like structure (reviewed in Hirano 2006;Huang et al 2005;Losada 2007;Nasmyth and Haering 2005). In most organisms, cohesin is loaded along chromosomes during telophase and is removed from the arms at the subsequent prophase.…”

Shugoshin regulates cohesion by driving relocalization of PP2A in Xenopus extracts

“…It entails the creation and maintenance of a physical linkage between the two copies of a chromosome that arise from the duplication process until their separation at the metaphase to anaphase transition. Cohesin, a ringshaped multiprotein complex conserved from yeast to human, is a major mediator of this linkage Nasmyth and Haering 2005). It consists of a heterodimer of SMC1 and SMC3 and two regulatory subunits, Scc1/Rad21 and Scc3/SA.…”

Functional links between Drosophila Nipped-B and cohesin in somatic and meiotic cells

“…Cohesin consists of a heterodimer of the Smc1 and Smc3 structural maintenance of chromosome proteins, and two other proteins, the α-kleisin Rad21 (Mcd1/Scc1) and Stromalin (SA/Scc3; reviewed in Hirano 2006;Nasmyth and Haering 2005). The Rad21 termini interact with the head domains of Smc1 and Smc3, forming a ringlike structure.…”

“…Its ring-like structure is the basis of the current cohesion models, in which cohesin encircles two sister chromatids or cohesin rings bound to two sisters interlock with each other (Hirano 2006;Huang et al 2005;Losada 2007;Nasmyth and Haering 2005). In some cases, a cohesin ring that encircles one sister may interact with proteins bound to the other sister to establish cohesion (Chang et al 2005).…”

“…Like the Nipped-B family, cohesin also has roles besides sister chromatid cohesion in meiosis, DNA repair, gene expression, and human development (reviewed in Dorsett 2007;Nasmyth and Haering 2005;Hagstrom and Meyer 2003;Hirano 2006;Revenkova and Jessberger 2006). Thus, a central question is whether regulation of cohesin also explains the functions of the Nipped-B family proteins in gene expression and meiosis.…”