Cohesion is a ring protein complex of the family of chromosome structure maintenance complexes (SMCs). From bacteria to humans, these protein rings are able to establish and maintain chromatin rings along chromosomes. Based on the results obtained in vitro on DNA molecules, it has been proposed that SMC complexes capture small DNA rings through their ring and then gradually expand them through their ATPase activity, which would cause them to move along the DNA molecule. In mammals, cohesion forms and maintains such cycles during the interphase of the cell cycle. Recent studies have shown that variations in the position and size of these rings affect and / or regulate processes such as transcription, recombination or even DNA repair. However, the molecular motors that control the widening and positioning of these loops along the chromosomes remain poorly defined.
To identify the DNA extrusion driver, scientists used a chromosomal conformation capture (Hi-C) approach to characterize chromosomal folding in yeast strains. Saccharomyces cerevisiae depleted in a controlled way in different proteins of the cohesion complex and accurately synchronized at different times of the cycle. By dissecting the effects of these depletions, they revealed that the Scc2 / NIPBL2 factor, which is known to load cohins on DNA, is also needed to promote DNA loop widening. Scc2 / NIPBL2 it plays this active role as a molecular motor stimulating the “ATPase” activity necessary for the displacement of cohins on the DNA. Furthermore, the scientists demonstrated that the activating function of Scc2 is repressed by binding of the helper protein Pds5 to cohins. This inhibition of the molecular motor by Pds5 results in the maintenance and stabilization of DNA loops at specific locations along the chromosomes. It therefore remained to determine how the cohesion complex changes from a dynamic shape to a stable shape during the expansion of the loops. The authors were able to demonstrate that acetylation of the Smc3 subunit by the Eco1 acetyltransferase promotes the binding of Pds5, to the detriment of Scc2, thus inhibiting the expansion of the loops.
These results were published alongside a study by Dr. Benjamin Rowland’s laboratory (Biology of Chromosomes, NKI) showing that these mechanisms are conserved in human cells.
To know more:
Acetylation of Smc3, Pds5 and Scc2 control translocase activity which establishes cohesion-dependent chromatin loops.
Bastié N, Chapard C, Dauban L, Gadal O, Beckouët F, Koszul R.
Nat Struct Mol Biol. June 16, 2022. doi: 10.1038 / s41594-022-00780-0.
The cohine acetylation cycle controls the chromatin cycle length through a PDS5A brake mechanism.
van Ruiten MS, van Gent D, Sedeño Cacciatore Á, Fauster A, Willems L, Hekkelman ML, Hoekman L, Altelaar M, Haarhuis JHI, Brummelkamp TR, de Wit E, Rowland BD.
Nat Struct Mol Biol. June 16, 2022: 10.1038 / s41594-022-00773-z.