An asymmetric SMC–kleisin bridge in prokaryotic condensin

Abstract

Eukaryotic structural maintenance of chromosomes (SMC)-kleisin complexes form large, ring-shaped assemblies that promote accurate chromosome segregation. Their asymmetric structural core comprises SMC heterodimers that associate with both ends of a kleisin subunit. However, prokaryotic condensin Smc-ScpAB is composed of symmetric Smc homodimers associated with the kleisin ScpA in a postulated symmetrical manner. Here, we demonstrate that Smc molecules have two distinct binding sites for ScpA. The N terminus of ScpA binds the Smc coiled coil, whereas the C terminus binds the Smc ATPase domain. We show that in Bacillus subtilis cells, an Smc dimer is bridged by a single ScpAB to generate asymmetric tripartite rings analogous to eukaryotic SMC complexes. We define a molecular mechanism that ensures asymmetric assembly, and we conclude that the basic architecture of SMC-kleisin rings evolved before the emergence of eukaryotes.

Condensin promotes the juxtaposition of DNA flanking its loading site in Bacillus subtilis

“…These models are also consistent with the ability of condensin to entrap DNA in vivo (Wilhelm et al 2015). The size of the pore in the condensin ring (>35 nm in the largest dimension) (Burmann et al 2013) could easily accommodate one or two DNA strands with attendant DNAbinding proteins, and supercoiled loops are likely flexible and dynamic enough to not obstruct movement (Fig. 7C).…”

“…B. subtilis condensin is composed of SMC, ScpA (kleisin), and the accessory protein ScpB (Britton et al 1998;Mascarenhas et al 2002;Soppa et al 2002). An SMC homodimer and ScpA form a tripartite ring that is similar in size, architecture, and intersubunit contacts to eukaryotic condensins (Hirano et al 2001;Burmann et al 2013;Kamada et al 2013). In bacteria, chromosome segregation occurs concomitant with DNA replication, and B. subtilis condensin plays a central role in the earliest step in this process: the compaction and resolution (or individualization) of newly replicated sister origins Wang et al 2014b).…”

Condensin II mutation causes T-cell lymphoma through tissue-specific genome instability

“…S1A). Based on available crystal structures (Bürmann et al 2013;Kamada et al 2013), the equivalent residue (I22) in prokaryotic condensins is largely buried and positioned within the first α helix of the kleisin subunit (ScpA) (Fig. 1A,B).…”

“…Evidence supporting this hypothesis recently arose from a gene network-based analysis of The Cancer Genome Atlas (TCGA) data set (Leiserson et al 2015). With the exception of SMC4, mutations in condensin subunits were not statistically enriched in tumor genomes when considered individually; however, statistical significance was reached when subunits were considered together as a (Bürmann et al 2013;Piazza et al 2014). The box indicates the region that is expanded in B.…”

“…The box indicates the region that is expanded in B. (B, right) Three-dimensional structure of the Smc head domain (SmcHead) and ScpA N-terminal domain (ScpA N ) from Bacillus subtilis (Protein Data Bank ID 3ZGX) (Bürmann et al 2013) is shown using PyMOL. The two noncontiguous sequence regions that together form the Smc ATPase head domain are color-coded in orange (SmcHead N ) and green (SmcHead C ), respectively, while the ScpA N domain fragment is shown in pink.…”