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Cohesin mediates DNA loop extrusion and sister chromatid cohesion by distinct mechanisms

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Homo sapiens

PROVIDER: GSE235772 | GEO | 2023/10/25

REPOSITORIES: GEO

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Cohesin mediates DNA loop extrusion and sister chromatid cohesion by distinct mechanisms [ChIP-seq]

Project description:Cohesin connects CTCF binding sites and other genomic loci in cis to form chromatin loops, and replicated DNA molecules in trans to mediate sister chromatid cohesion. Whether cohesin uses distinct or related mechanisms to perform these functions is unknown. Here we describe a cohesin hinge mutant, which can extrude DNA into loops but is unable to mediate cohesion. Our results suggest that the latter defect arises during cohesion establishment. The observation that cohesin’s cohesion and loop extrusion activities can be separated indicates that cohesin uses distinct mechanisms to perform these two functions. Unexpectedly, the same hinge mutant can also not be stopped by CTCF boundaries as well as wildtype cohesin. This suggests that cohesion establishment and cohesin’s interaction with CTCF boundaries depend on related mechanisms and raises the possibility that both require transient hinge opening to entrap DNA inside the cohesin ring.

2023-10-25 | GSE235770 | GEO

Cohesin mediates DNA loop extrusion and sister chromatid cohesion by distinct mechanisms [Hi-C]

2023-10-25 | GSE235771 | GEO

Cohesin mediates DNA loop extrusion and sister chromatid cohesion by distinct mechanisms

Project description:Cohesin mediates DNA loop extrusion and sister chromatid cohesion by distinct mechanisms

| PRJNA987590 | ENA

Cohesin mediates DNA loop extrusion and sister chromatid cohesion by distinct mechanisms [ChIP-seq]

Project description:Cohesin mediates DNA loop extrusion and sister chromatid cohesion by distinct mechanisms [ChIP-seq]

| PRJNA987600 | ENA

Cohesin mediates DNA loop extrusion and sister chromatid cohesion by distinct mechanisms [Hi-C]

Project description:Cohesin mediates DNA loop extrusion and sister chromatid cohesion by distinct mechanisms [Hi-C]

| PRJNA987599 | ENA

Sister chromatid cohesion halts DNA loop expansion

Project description:Eukaryotic genomes are folded into DNA loops mediated by SMC complexes, like cohesin, condensin and Smc5/6. This organization regulates different DNA related processes along the cell cycle such as transcription, recombination, segregation and DNA repair. During G2/M phases, SMC complexes mediated DNA loops coexist with cohesin complexes involved in sister chromatid cohesion (SCC). It remains unknown whether SCC and DNA loop expansion influence each other and if they cooperate to regulate DNA-related processes. Here we show that SCC is indeed a barrier to DNA loop expansion mediated by cohesin in G2.

2024-01-30 | GSE237031 | GEO

Cohesin-mediated DNA loop extrusion resolves sister chromatids in G2 phase

Project description:Genetic information is stored in linear DNA molecules, which are highly folded inside cells. DNA replication along the folded template path yields two sister chromatids that initially occupy the same nuclear region in an intertwined arrangement. Dividing cells must disentangle and condense the sister chromatids into separate bodies such that a microtubule-based spindle can move them to opposite poles. While the spindle-mediated transport of sister chromatids has been studied in detail, the chromosome-intrinsic mechanics pre-segregating sister chromatids have remained elusive. Here, we show that human sister chromatids resolve extensively already during interphase, in a process dependent on the loop-extruding activity of cohesin, but not that of condensins. Increasing cohesin's looping capability increases sister DNA resolution in interphase nuclei to an extent normally seen only during mitosis, despite the presence of abundant arm cohesion. That cohesin can resolve sister chromatids so extensively in the absence of mitosis-specific activities indicates that DNA loop extrusion is a generic mechanism for segregating replicated genomes, shared across different Structural Maintenance of Chromosomes (SMC) protein complexes in all kingdoms of life.

| S-SCDT-10_15252-EMBJ_2023113475 | biostudies-other

Sister chromatid cohesion halts DNA loop expansion

Project description:Sister chromatid cohesion halts DNA loop expansion

| PRJNA993572 | ENA

MCM2-7-dependent cohesin loading during S phase promotes sister-chromatid cohesion.

Project description:DNA replication transforms cohesin rings dynamically associated with chromatin into the cohesive form to establish sister-chromatid cohesion. Here, we show that, in human cells, cohesin loading onto chromosomes during early S phase requires the replicative helicase MCM2-7 and the kinase DDK. Cohesin and its loader SCC2/4 (NIPBL/MAU2 in humans) associate with DDK and phosphorylated MCM2-7. This binding does not require MCM2-7 activation by CDC45 and GINS, but its persistence on activated MCM2-7 requires fork-stabilizing replisome components. Inactivation of these replisome components impairs cohesin loading and causes interphase cohesion defects. Interfering with Okazaki fragment processing or nucleosome assembly does not impact cohesion. Therefore, MCM2-7-coupled cohesin loading promotes cohesion establishment, which occurs without Okazaki fragment maturation. We propose that the cohesin-loader complex bound to MCM2-7 is mobilized upon helicase activation, transiently held by the replisome, and deposited behind the replication fork to encircle sister chromatids and establish cohesion.

| S-EPMC5897099 | biostudies-literature

Sister chromatid cohesion establishment during DNA replication termination.

Project description:Newly copied sister chromatids are tethered together by the cohesin complex, but how sister chromatid cohesion coordinates with DNA replication is poorly understood. Prevailing models suggest that cohesin complexes, bound to DNA before replication, remain behind the advancing replication fork to keep sister chromatids together. By visualizing single replication forks colliding with preloaded cohesin complexes, we find that the replisome instead pushes cohesin to where a converging replisome is met. Whereas the converging replisomes are removed during DNA replication termination, cohesin remains on nascent DNA and provides cohesion. Additionally, we show that CMG (CDC45-MCM2-7-GINS) helicase disassembly during replication termination is vital for proper cohesion in budding yeast. Together, our results support a model wherein sister chromatid cohesion is established during DNA replication termination.

| S-EPMC7615807 | biostudies-literature

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