Sister chromatid cohesion is mediated by individual cohesin complexes

Abstract

Eukaryotic genomes are organized by loop extrusion and sister chromatid cohesion, both mediated by the multimeric cohesin protein complex. Understanding how cohesin holds sister DNAs together, and how loss of cohesion causes age-related infertility in females, requires knowledge as to cohesin’s stoichiometry in vivo. Using quantitative super-resolution imaging, we identified two discrete populations of chromatin-bound cohesin in postreplicative human cells. Whereas most complexes appear dimeric, cohesin that localized to sites of sister chromatid cohesion and associated with sororin was exclusively monomeric. The monomeric stoichiometry of sororin:cohesin complexes demonstrates that sister chromatid cohesion is conferred by individual cohesin rings, a key prediction of the proposal that cohesion arises from the co-entrapment of sister DNAs.

Extensive mutual influences of SMC complexes shape 3D genome folding

“…Together, these findings highlight the non-overlapping functionalities of the two cohesin forms. Our results are consistent with studies showing distinct mechanisms for cohesin mediated loop extrusion and chromatid cohesion 14,40 .…”

“…To decipher the potential influence of condensin on cohesive-cohesin, we sought to map the binding profile of Sororin, which selectively marks cohesive-cohesin 14,32 , in the absence versus the presence of condensin. Since Sororin is typically evicted from mitotic chromosome arms by CDK1/Aurora B mediated phosphorylation, we employed a previously characterized mutant form of Sororin, harboring nine evolutionarily conserved phosphosites mutated to alanine 34,35 (Extended Data Fig.…”

“…By maintaining these structures, extrusive-cohesin can facilitate or insulate contacts between gene promoters and distal enhancers, thereby influencing transcription 10 . During S-phase, a distinct set of cohesin complexes emerges to topologically encircle replicated DNA strands, thereby mediating cohesion between sister-chromatids [11][12][13][14] . This cohesive form of cohesin may appear by de-novo loading during or after DNA replication or through conversion of pre-existing chromatin-associated cohesin molecules [15][16][17] .…”

Quantitative imaging of loop extruders rebuilding interphase genome architecture after mitosis

“…Using structured illumination microscopy of the isoform-shared Cohesin subunit RAD21, it was recently reported that the majority of the loop-extruding Cohesin is present in dimers or multimers (Ochs et al, 2024). Consistent with this finding, our STED super-resolution imaging of isoform-specific Cohesin subunits revealed that the less abundant Cohesin-STAG1 is present as a monomer, but that the more abundant isoform Cohesin-STAG2 undergoes dimerization on chromatin in later G1 in a concentration dependent manner.…”