Cohesin acetyltransferase Esco2 is a cell viability factor and is required for cohesion in pericentric heterochromatin

Whelan, Gabriela; Kreidl, Emanuel; Wutz, Gordana; Egner, Alexander; Peters, Jan‐Michael; Eichele, Gregor

doi:10.1038/emboj.2011.381

Cited by 103 publications

(152 citation statements)

References 54 publications

(74 reference statements)

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“…This idea is also consistent with the identification of homozygous mutations in the gene encoding the CoAT Esco2 (establishment of cohesion homolog 2) as the cause of RBS (Vega et al, 2005). Esco2 is essential for cohesion establishment in pericentric heterochromatin (Whelan et al, 2012), which explains the loss of pericentromeric cohesion in chromosomes from individuals with RBS. Intriguingly, Esco2 deficiency in mice results in very early embryonic lethality (Whelan et al, 2012), maybe because the acrocentric nature of mouse chromosomes make them more prone to mis-segregation in the absence of pericentric cohesion.…”

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confidence: 69%

Cohesin in development and disease

2013

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SummaryCohesin is a ring-shaped complex, conserved from yeast to human, that was named for its ability to mediate sister chromatid cohesion. This function is essential for chromosome segregation in both mitosis and meiosis, and also for DNA repair. In addition, more recent studies have shown that cohesin influences gene expression during development through mechanisms that likely involve DNA looping and interactions with several transcriptional regulators. Here, we provide an overview of how cohesin functions, highlighting its role both in development and in disease. Key words: Chromatin loops, Cohesion, Cohesinopathies IntroductionThe development of a complex multicellular organism from the fusion of two haploid cells requires two fundamental processes:one is cell proliferation, in order to grow; the other is cell differentiation, in order to generate specialized cells for tissues and organs. The cohesin complex plays key roles in both these processes. Cohesin was originally identified as the mediator of sister chromatid cohesion. It establishes a physical link between the two sister chromatids from the moment they arise from the replication fork. This link is essential for efficient DNA repair by homologous recombination during S/G2, and for proper chromosome alignment and segregation in mitosis. In this way, cohesin ensures the accurate transmission of genetic material during cell proliferation. Regarding cell differentiation, it is clear that what defines a cell type is not its genome, but how this genome is used. Increasing evidence supports the importance of higher order chromatin structure in the temporal and spatial regulation of transcription. We are only beginning to understand how the spatial organization of chromatin affects gene expression, but cohesin is emerging as an important contributor to such organization. Here, and in the accompanying poster, we briefly review our current knowledge of cohesin and its different functions, and focus on how these functions contribute to embryonic development. Development 140, 3715-3718 (2013) DEVELOPMENT 3716The cohesin complex Cohesin consists of four subunits -Smc1, Smc3, Scc1/Rad21 and Scc3/SA -arranged in a ring-shaped structure. Smc1 and Smc3 belong to the structural maintenance of chromosomes (SMC) family of chromosomal ATPases that also includes the core subunits of condensin and of the Smc5/6 complex. These complexes are conserved from yeast to human, and SMC-like proteins contribute to chromosome organization and dynamics in bacteria and archaea (Hirano, 2005). Scc1/Rad21 belongs to the kleisin protein family and interacts with both Smc1 and Smc3 to close the ring. The Scc3/SA subunit in somatic vertebrate cells can be either SA1 or SA2, although additional variants for SA and other subunits also exist in meiotic cells.The regulation of cohesin during the cell cycle Cohesin topologically embraces chromatin fiber(s) within its ringshaped structure (Nasmyth, 2011). The complex is recruited to chromatin during G1 in a process that requires the cohesini...

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confidence: 69%

Cohesin in development and disease

2013

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“…Thus, although there may be some redundancy of function between Eco1 and Eco2, embryonic development may be critically dependent on Eco2. Recent analyses in both fish and mice are consistent with a dependence on Esco2 in the early embryo (25,39).…”

Section: Discussionmentioning

confidence: 61%

“…Acetylates Smc3-In somatic cells both Esco1 and Esco2 contribute to Smc3 acetylation (5,25). However, in the early frog embryo XEco1 is at very low levels, only rising near the mid-blastula transition (13), suggesting that XEco2 alone provides Smc3 acetylation in the early embryo.…”

Section: Xeco2mentioning

confidence: 99%

Cohesin Acetylation Promotes Sister Chromatid Cohesion Only in Association with the Replication Machinery

Song

Lafont

Chen

et al. 2012

Journal of Biological Chemistry

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Background:The conversion of cohesin to an active form requires DNA replication and acetylation of the Smc3 subunit of the complex by Eco acetyltransferases. Results: Cohesin acetylation occurs both when replication is blocked and after replication is complete but only ensures cohesion in association with the replication machinery. Conclusion: The context of cohesin acetylation is critical to cohesion establishment. Significance: Acetylation and cohesion establishment are regulated differently in yeast and vertebrates.

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“…Loss of WPL1 activity in yeast has been linked to interallelic recombination, chromosomal amplification, and aneuploidy at rates 17-fold higher than wild-type colonies (Covo et al, 2014a(Covo et al, , 2014b. Likewise, point mutations in human, mouse, and yeast CTF7/Eco1 orthologs result in hypersensitivity to DNA damaging agents (van der Lelij et al, 2009;Lu et al, 2010;Whelan et al, 2012). While further experiments are required to directly analyze mitosis in leaf cells, the conclusion that mitosis is normal in wapl1-1 wapl2 ctf7 plants is consistent with our results showing that inactivation of CTF7 and WAPL together suppresses the mitotic defects associated with either of the individual mutations in root cells.…”

Section: Ctf7 and Wapl Are Essential For Embryo Development But Not mentioning

confidence: 99%

The Opposing Actions of Arabidopsis CHROMOSOME TRANSMISSION FIDELITY7 and WINGS APART-LIKE1 and 2 Differ in Mitotic and Meiotic Cells

Bolaños-Villegas

Mitra

et al. 2016

Plant Cell

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Sister chromatid cohesion, which is mediated by the cohesin complex, is essential for the proper segregation of chromosomes during mitosis and meiosis. Stable binding of cohesin with chromosomes is regulated in part by the opposing actions of CTF7 (CHROMOSOME TRANSMISSION FIDELITY7) and WAPL (WINGS APART-LIKE). In this study, we characterized the interaction between Arabidopsis thaliana CTF7 and WAPL by conducting a detailed analysis of wapl1-1 wapl2 ctf7 plants. ctf7 plants exhibit major defects in vegetative growth and development and are completely sterile. Inactivation of WAPL restores normal growth, mitosis, and some fertility to ctf7 plants. This shows that the CTF7/WAPL cohesin system is not essential for mitosis in vegetative cells and suggests that plants may contain a second mechanism to regulate mitotic cohesin. WAPL inactivation restores cohesin binding and suppresses ctf7-associated meiotic cohesion defects, demonstrating that WAPL and CTF7 function as antagonists to regulate meiotic sister chromatid cohesion. The ctf7 mutation only had a minor effect on wapl-associated defects in chromosome condensation and centromere association. These results demonstrate that WAPL has additional roles that are independent of its role in regulating chromatin-bound cohesin.

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Cohesin acetyltransferase Esco2 is a cell viability factor and is required for cohesion in pericentric heterochromatin

Cited by 103 publications

References 54 publications

Cohesin in development and disease

Cohesin in development and disease

Cohesin Acetylation Promotes Sister Chromatid Cohesion Only in Association with the Replication Machinery

The Opposing Actions of Arabidopsis CHROMOSOME TRANSMISSION FIDELITY7 and WINGS APART-LIKE1 and 2 Differ in Mitotic and Meiotic Cells

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