Closing the ring: links between SMC proteins and chromosome partitioning, condensation, and supercoiling.

The paper by Sawitzke and Austin (1) ties together all three conclusions. Their work concerns the Muk (from the Japanese mukaku, meaning anucleate) protein complex of Escherichia coli, which was discovered and characterized by Hiraga and coworkers (2). Mutations in any of the three muk genes, mukB, mukE, and mukF, disrupt chromosome segregation such that many progeny have missing or incomplete chromosomes that have been guillotined by septation. What links this fate of muk2 bacteria to our story is that their chromosomes are decondensed (3) and that MukB is the structural and functional analogue of the ubiquitous SMC family of proteins (4). These huge molecules form coiled-coil dimers that, along with associated proteins, are thought to bind DNA segments separated by as much as 1,000 Å and then to contract the intervening DNA at the expense of ATP (5). Sawitzke and Austin show that the severity of the Muk phenotype can be controlled by changing the level of supercoiling in the cell. The harsh consequences of being Mukless are suppressed by just a modest increase in chromosomal supercoiling, and muk2 cells are hypersensitive to gyrase inhibitors. The authors conclude that Muk and supercoiling cooperate in condensing DNA, which drives partitioning. These findings fit beautifully with those from biophysics to cell biology in a wide array of organisms. DNA Condensation. To put this work in context, we need first to review the properties of DNA condensation. DNA is vastly longer than the space assigned to it because of the shortsightedness of evolution in fashioning a linear genetic code. The needed condensation has been traditionally described one-dimensionally as the ratio of DNA length to the diameter of its container, a nucleus, or nucleoid. There is a more biophysical way of quantifying the space crunch. The persistence length of DNA (a) is so small compared with its total length (L) that its natural low energy conformation is already substantially condensed [dimensions of (aL)1y2]. Moreover, DNA must be condensed not in one dimension but in three. Instead of linear compaction, a better way to judge condensation is the volume reduction of a random coil of free DNA to its final volume in a cell (refs. 6 and 7; Table 1). The amount of DNA compaction increases with genome size and is on the order of 103 for E. coli and 105 for humans. Three mechanisms of in vivo condensation are illustrated in Fig. 1. Two of these, (2) supercoiling of DNA free in solution (ref. 8; Fig. 1 A and D) and the constrained DNA supercoiling in nucleosomes (ref. 9; Fig. 1B) are well understood physically and physiologically. The third mechanism has been discovered only recently and is at the core of our story today. This is the (1) supercoiling buttressed by 13S condensin, the key SMC protein complex of frogs (ref. 10; Fig. 1C).