Cohesin Can Remain Associated with Chromosomes during DNA Replication

Rhodes, James; Haarhuis, Judith H.I.; Grimm, Jonathan B.; Rowland, Benjamin D.; Lavis, Luke D.; Nasmyth, K

doi:10.1016/j.celrep.2017.08.092

Cited by 61 publications

(36 citation statements)

References 24 publications

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“…This does not require that replisomes move through cohesin or new cohesin loading behind the fork as proposed in other models (Uhlmann 2016, Villa-Hernández andBermejo 2018). It is consistent with the finding that cohesin can remain chromosomebound and establish cohesion during DNA replication in the absence of the Wapl removal factor (Rhodes et al 2017).…”

Section: Sister Chromatid Cohesionsupporting

confidence: 90%

Cohesin occupancy and composition at enhancers and promoters are linked to DNA replication origin proximity inDrosophila

Pherson

Misulovin

Gause

et al. 2019

Preprint

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Cohesin consists of the Smc1-Smc3-Rad21 tripartite ring and the SA protein that interacts with Rad21. The Nipped-B protein loads cohesin topologically around chromosomes to mediate sister chromatid cohesion and facilitate long-range control of gene transcription. It is largely unknown how Nipped-B and cohesin associate specifically with gene promoters and transcriptional enhancers, or how sister chromatid cohesion is established. Here we use genome-wide chromatin immunoprecipitation in Drosophila cells to show that SA and the Fs(1)h (BRD4) BET domain protein help recruit Nipped-B and cohesin to enhancers and DNA replication origins, while the MED30 subunit of the Mediator complex directs Nipped-B and Rad21 to promoters. All enhancers and their neighboring promoters are close to DNA replication origins and bind SA with proportional levels of cohesin subunits. Most promoters are far from origins and lack SA, but bind Nipped-B and Rad21 with sub-proportional amounts of Smc1, indicating that they bind SA-deficient cohesin part of the time. Genetic data confirm that Nipped-B and Rad21 function together with Fs(1)h in vivo to facilitate Drosophila development. These findings demonstrate that Nipped-B and cohesin are differentially targeted to enhancers and promoters and suggest models for how SA and DNA replication help establish sister chromatid cohesion and facilitate enhancer-promoter communication. They indicate that SA is not an obligatory cohesin subunit but a factor that controls cohesin location on chromosomes.

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Section: Sister Chromatid Cohesionsupporting

confidence: 90%

Cohesin occupancy and composition at enhancers and promoters are linked to DNA replication origin proximity inDrosophila

Pherson

Misulovin

Gause

et al. 2019

Preprint

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“…The interaction between Scc2 and chromatin was measured by bleaching a circle of Scc2 JF549 fluorescence and measuring fluorescence recovery after photobleaching (FRAP) ( Figure 1e,f ). FRAP experiments were performed in the presence of an unlabelled HaloTag ligand to prevent relabeling of newly synthesised Halo-Scc2 ( Rhodes et al, 2017 ). Scc2 JF549 FRAP curves did not fit a single exponential function ( Figure 1—figure supplement 1 ).…”

Section: Resultsmentioning

confidence: 99%

Scc2/Nipbl hops between chromosomal cohesin rings after loading

Rhodes

Mazza

Nasmyth

et al. 2017

eLife

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The cohesin complex mediates DNA-DNA interactions both between (sister chromatid cohesion) and within chromosomes (DNA looping). It has been suggested that intra-chromosome loops are generated by extrusion of DNAs through the lumen of cohesin’s ring. Scc2 (Nipbl) stimulates cohesin’s ABC-like ATPase and is essential for loading cohesin onto chromosomes. However, it is possible that the stimulation of cohesin’s ATPase by Scc2 also has a post-loading function, for example driving loop extrusion. Using fluorescence recovery after photobleaching (FRAP) and single-molecule tracking in human cells, we show that Scc2 binds dynamically to chromatin, principally through an association with cohesin. Scc2’s movement within chromatin is consistent with a 'stop-and-go' or 'hopping' motion. We suggest that a low diffusion coefficient, a low stoichiometry relative to cohesin, and a high affinity for chromosomal cohesin enables Scc2 to move rapidly from one chromosomal cohesin complex to another, performing a function distinct from loading.

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“…The relative importance of these two effects may depend on the cell type, as for HeLa cells we find complete rescue of fiber track lengths by mirin, whereas in MEFs the rescue is only partial, suggesting that in the human cells the main effect is on the fork protection pathway, whereas in mouse cells both effects are in place. Cohesin transfer may involve a transient opening of the ring in concert with replisome components, a mechanism pro-posed to explain cohesion establishment during DNA replication (19,20). When this transfer is impaired by depletion of PDS5 or WAPL, or when cohesin is absent, recruitment of fork protection proteins is reduced and the stability of the stalled fork is compromised.…”

Section: Cohesin Dynamics and Dna Replicationmentioning

confidence: 99%

PDS5 proteins are required for proper cohesin dynamics and participate in replication fork protection

Morales

Ruiz‐Torres

Rodríguez‐Acebes

et al. 2020

Journal of Biological Chemistry

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Edited by Patrick Sung Cohesin is a chromatin-bound complex that mediates sister chromatid cohesion and facilitates long-range interactions through DNA looping. How the transcription and replication machineries deal with the presence of cohesin on chromatin remains unclear. The dynamic association of cohesin with chromatin depends on WAPL cohesin release factor (WAPL) and on PDS5 cohesin-associated factor (PDS5), which exists in two versions in vertebrate cells, PDS5A and PDS5B. Using genetic deletion in mouse embryo fibroblasts and a combination of CRISPRmediated gene editing and RNAi-mediated gene silencing in human cells, here we analyzed the consequences of PDS5 depletion for DNA replication. We found that either PDS5A or PDS5B is sufficient for proper cohesin dynamics and that their simultaneous removal increases cohesin's residence time on chromatin and slows down DNA replication. A similar phenotype was observed in WAPL-depleted cells. Cohesin down-regulation restored normal replication fork rates in PDS5-deficient cells, suggesting that chromatin-bound cohesin hinders the advance of the replisome. We further show that PDS5 proteins are required to recruit WRN helicase-interacting protein 1 (WRNIP1), RAD51 recombinase (RAD51), and BRCA2 DNA repair associated (BRCA2) to stalled forks and that in their absence, nascent DNA strands at unprotected forks are degraded by MRE11 homolog double-strand break repair nuclease (MRE11). These findings indicate that PDS5 proteins participate in replication fork protection and also provide insights into how cohesin and its regulators contribute to the response to replication stress, a common feature of cancer cells. This work was supported by the Spanish Ministry of Economy and Competitiveness and FEDER Grants BFU2013-48481-R and BFU2016-79841-R (to A. L.) and BFU2016-80402-R (to J. M.) and by FPI "Severo Ochoa" fellowships (to C. M. and M. R.-T.). This work was also supported by funding from Boehringer Ingelheim Fonds (to M. R.-T.). The authors declare that they have no conflicts of interest with the contents of this article. Author's Choice-Final version open access under the terms of the Creative Commons CC-BY license. This article contains Figs. S1-S5 and Tables S1 and S2.

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Cohesin Can Remain Associated with Chromosomes during DNA Replication

Cited by 61 publications

References 24 publications

Cohesin occupancy and composition at enhancers and promoters are linked to DNA replication origin proximity inDrosophila

Cohesin occupancy and composition at enhancers and promoters are linked to DNA replication origin proximity inDrosophila

Scc2/Nipbl hops between chromosomal cohesin rings after loading

PDS5 proteins are required for proper cohesin dynamics and participate in replication fork protection

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