At the heart of the chromosome: SMC proteins in action

Abstract

Structural maintenance of chromosomes (SMC) proteins are ubiquitous in organisms from bacteria to humans, and function as core components of the condensin and cohesin complexes in eukaryotes. SMC proteins adopt a V-shaped structure with two long arms, each of which has an ATP-binding head domain at the distal end. It is important to understand how these uniquely designed protein machines interact with DNA strands and how such interactions are modulated by the ATP-binding and -hydrolysis cycle. An emerging idea is that SMC proteins use a diverse array of intramolecular and intermolecular protein-protein interactions to actively fold, tether and manipulate DNA strands.

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.…”

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.…”

Double SMCHD1 variants in FSHD2: the synergistic effect of two SMCHD1 variants on D4Z4 hypomethylation and disease penetrance in FSHD2

“…14 SMCHD1 is an atypical member of the SMC gene superfamily, a family of proteins which is involved in chromosome condensation and cohesion, genome maintenance and gene regulation. [17][18][19] Chromatin immunoprecipitation studies showed the presence of SMCHD1 on the D4Z4 array and its reduced binding to D4Z4 in SMCHD1 mutation carriers. 14 SMCHD1 variants can also modify the disease severity in FSHD1 families, explaining some of the clinical variability seen in FSHD.…”