How does the centromere-binding protein ParB interact with DNA to recruit Structural Maintenance of Chromosomes?

Stemming directly from their work on the Structural Maintenance of Chromosomes (SMC), the Tung Le group discovered that the centromere-binding protein ParB recruits SMC onto DNA by a direct protein-protein interaction.

In this strand of research, the group are investigating the properties of ParB to understand how SMC is first recruited onto the DNA to initiate folding of the chromosome.

To do this they investigated the genome-wide distribution of ParB on the Caulobacter chromosome using a combination of ChIP-seq and IDAP-seq to discover at least five ParB-binding parS sites that closely cluster ~8 kb from the origin of replication, and defined these sites to single-nucleotide resolution.

The group showed that ParB is also capable of binding DNA non-specifically to form a “daisy chain” of ParB molecules emanating outwards from its parS nucleation site, and this is mediated by a protein-protein “handshaking” between neighboring ParB dimers.

From there they hypothesised that this unusual “spreading” property of ParB is important to load enough SMC molecules onto the chromosome at a given time, which they are actively investigating.

The biological significance is that the rate of SMC loading might dictate how large the DNA loop being formed is, and how compacted the chromosome is. If correct, this would fit well with recent findings that altering the unloading rate of cohesin dramatically impacts DNA loop formation in eukaryotes (Haarhuis et al 2017 Cell, Gassler et al 2017 EMBOJ, and Wutz et al 2017 EMBOJ).