SMC proteins

Abstract

What are SMCs? The Structural Maintenance of Chromosomes (SMC) proteins are a family of chromosomal ATPases highly conserved among the three phyla of life. First came to prominence… In 1993, when the first SMC protein was characterised as a gene product required for proper chromosome segregation in budding yeast. The following year, using a variety of approaches, a number of related proteins were identified in different organisms, laying the foundation of the SMC superfamily. What do SMCs look like? The SMC proteins are large polypeptides, each spanning 1000–1500 amino acids. They form dimers in which two anti-parallel coiled-coil arms are connected by a flexible hinge (Figure 1). The distal end of each arm constitutes an ATP-binding domain. How many SMCs in a single species? Whereas both the archaeal and bacterial genomes contain only one SMC gene, six distinct SMC paralogues are found in individual eukaryotes. Each of the eukaryotic SMCs has a specific dimer partner – SMC1–3, SMC2–4 and SMC5–6. What do SMCs do in the cell? Each SMC dimer forms a functional complex with a distinct set of non-SMC subunits. SMC1–3 forms the core of the cohesin complex that functions in sister chromatid cohesion (Figure 1, left). SMC2–4 forms part of the condensin complex, a key player in mitotic chromosome condensation (Figure 1, right). Bacterial SMC is involved in chromosome partitioning and is thought to be an ancestor of condensin and cohesin. The SMC5–6 complex is implicated in DNA repair and checkpoint responses. Do they have other functions? Yes… In Caenorhabditis elegans, an SMC4 variant associates with the canonical SMC2 to form a condensin-like complex that regulates chromosome-wide gene expression as part of the worm's dosage compensation mechanism. In many organisms, meiosis-specific subunits bind to SMC1–3. These play a crucial role in meiotic chromosome segregation. How do SMCs work? That is the million-dollar question in the field. Of particular interest is to understand how the two-armed structure – which is approximately 100 nm long when it's open! – captures DNA, and how these interactions are modulated by ATP binding and hydrolysis. Condensin is able to introduce positive supercoils into DNA by using the energy of ATP hydrolysis. Further studies are required to understand the functional diversity of the SMCs. Can we live without SMCs? No! Loss of any single SMC protein in budding yeast is lethal. Given their fundamental role in maintaining genomic stability, it is of future interest to determine whether loss or mutation of SMCs is associated with tumour formation or developmental disorders in mammals. If you have an interesting viewpoint on any issue relating to biological research that you would like to put before a general readership in a My Word article of about 800–900 words, email your proposal to: [email protected] If you have an interesting viewpoint on any issue relating to biological research that you would like to put before a general readership in a My Word article of about 800–900 words, email your proposal to: [email protected]