The Structure of Chromosomes:- Condensed Chromosome Structures Are Maintained by SMC Proteins
A third major class of chromatin proteins, in addition to the histones and topoisomerases, is the SMC proteins (structural maintenance of chromosomes). The primary structure of SMC proteins consists of five distinct do mains (Fig. 1a). The amino- and carboxyl-terminal globular domains, N and C, each of which has part of an ATP hydrolytic site, are connected by two regions of-helical coiled-coil motifs that are joined by a hinge domain. The proteins are generally dimeric, forming a V-shaped complex that is thought to be tied together through their hinge domains (Fig. 1b). One N and one C domain come together to form a complete ATP hydrolytic site at each end of the V.
Proteins in the SMC family are found in all types of organisms, from bacteria to humans. Eukaryotes have two major types, cohesins and condensins. The cohesins play a substantial role in linking together sister chromatids immediately after replication and keeping them together as the chromosomes condense to metaphase. This linkage is essential if chromosomes are to segregate properly at cell division. The detailed mechanism by which cohesins link sister chromosomes, and the role of ATP hydrolysis, are not yet understood. The condensins are essential to the condensation of chromosomes as cells enter mitosis. In the laboratory, condensins bind to DNA in a manner that creates positive supercoils; that is, condensin binding causes the DNA to become overwound, in contrast to the under winding induced by the binding of nucleosomes. It is not yet clear how this helps to compact the chromatin, although one possibility is presented in Figure 2.
FIGURE 1 Structure of SMC proteins. (a) The five domains of the SMC primary structure. N and C denoted the amino-terminal and carboxyl-terminal domains, respectively. (b) Each polypeptide is folded so that the two coiled-coil domains wrap around each other and the N and C domains come together to form a complete ATP binding site. Two of these domains are linked at the hinge region to form the dimeric V-shaped molecule. (c) Electron micrograph of SMC proteins from Bacillus subtilis.
FIGURE 2 Model for the effect of condensins on DNA super coiling. Binding of condensins to a closed-circular DNA in the presence of topoisomerase I leads to the production of positive supercoils (+). Wrapping of the DNA about the condensin introduces positive supercoils because it wraps in the opposite sense to a solenoidal supercoil. The compensating negative supercoils (-) that appear elsewhere in the DNA are then relaxed by topoisomerase I. In the chromosome, it is the wrapping of the DNA about condensin that may contribute to DNA condensation.
