How does Structural Maintenance of Chromosomes (SMC) protein interactions with DNA to organise bacterial chromosomes?

Structural Maintenance of Chromosomes (SMC) proteins, also known as cohesins and condensins in eukaryotes, are crucial for chromosome organisation in all living organisms, but how SMC translocates on a protein-laden chromosome is poorly investigated.

Whether SMC impacts DNA-translocating proteins such as RNA polymerase and is, in turn, influenced by such proteins, is not well understood. How different cellular processes share the same DNA but avoid, or resolve, conflicts is a question that arises in all cells and all domains of life.

Tung Le group’s recent study provided experimental evidence that the translocation of bacterial SMC on the chromosome is strongly influenced by RNA polymerase.

The group showed that highly-transcribed genes oriented to collide head-on with translocating SMC slowing down and potentially stopping SMC translocation. This might have contributed to the evolutionary selection for highly-transcribed genes to be co-oriented with the direction of DNA replication and SMC movement.

Broadly, the group’s work demonstrated a tight interdependence of bacterial chromosome organisation and the highly non-random global pattern of transcription. Furthermore, they demonstrated that the translocation of bacterial SMC is directional, starting at the bacterial centromere site parS and moving progressively towards the replication terminus, extruding out DNA in a loop as a result of this directional movement.

The finding that bacterial SMC translocation is directional has significant implications for how eukaryotic cohesins extrude DNA loops (Rao et al 2015 Cell, Sanborn et al 2015 PNAS, Fudenberg et al 2016 Cell Rep).

Caulobacter crescentus as model organism

The Le group’s findings were greatly aided by using Caulobacter as a model system.

Caulobacter is easily synchronised, enabling us to generate genome-wide data for a homogenous population of G1-phase cells that each contain a single chromosome.

As there is no active DNA replication in the G1 cells, they were able to isolate and specifically study the effect of transcription on SMC translocation and global chromosome organisation, without confounding effects from replication-transcription conflicts.