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

Abstract

A gratifying story is emerging on how  the complementary strands of the DNA double helix are unlinked and partitioned after replication with astonishing accuracy as finished chromosomes to daughter cells. There are three key conclusions: 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 muk − 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 A 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 muk − 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 …