A Molecular Determinant for the Establishment of Sister Chromatid Cohesion

Ünal, Elçin; Heidinger-Pauli, Jill M.; Kim, Woong; Guacci, Vincent; Onn, Itay; Gygi, Steven P.; Koshland, Douglas

doi:10.1126/science.1157880

Cited by 436 publications

(451 citation statements)

References 30 publications

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“…Early studies had pointed out the involvement of a specialized class of acetyltransferases (Eco1/Ctf7 in budding yeast; ESCO1 and ESCO2 in vertebrates) (Ivanov et al 2002;Bellows et al 2003). A series of subsequent studies showed that two conserved residues in SMC3 are the essential targets of the Eco1/ESCO1 acetyltransferase, and the acetylation reactions are indeed essential for cohesion establishment in budding yeast (Ben-Shahar et al 2008;Unal et al 2008) and humans (Zhang et al 2008). More recently, the deacetylase that reverses this reaction has been identified as Hos1 in budding yeast (Beckouët et al 2010;Borges et al 2010;Xiong et al 2010) and HDAC8 in humans (Deardorff et al 2012).…”

Section: Cohesin Establishes Sister Chromatid Cohesion During S Phasementioning

confidence: 99%

Chromosome Dynamics during Mitosis

Hirano

2015

Cold Spring Harb Perspect Biol

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The primary goal of mitosis is to partition duplicated chromosomes into daughter cells. Eukaryotic chromosomes are equipped with two distinct classes of intrinsic machineries, cohesin and condensins, that ensure their faithful segregation during mitosis. Cohesin holds sister chromatids together immediately after their synthesis during S phase until the establishment of bipolar attachments to the mitotic spindle in metaphase. Condensins, on the other hand, attempt to "resolve" sister chromatids by counteracting cohesin. The products of the balancing acts of cohesin and condensins are metaphase chromosomes, in which two rod-shaped chromatids are connected primarily at the centromere. In anaphase, this connection is released by the action of separase that proteolytically cleaves the remaining population of cohesin. Recent studies uncover how this series of events might be mechanistically coupled with each other and intricately regulated by a number of regulatory factors.

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Section: Cohesin Establishes Sister Chromatid Cohesion During S Phasementioning

confidence: 99%

Chromosome Dynamics during Mitosis

Hirano

2015

Cold Spring Harb Perspect Biol

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“…An antiestablishment complex consisting of Wings Apart-Like protein (WAPL)/Rad61 and Pds5 is required to maintain cohesion during G2/M by stabilizing the interaction between cohesin and the chromosomes (Panizza et al, 2000;Losada et al, 2005;Gandhi et al, 2006). While the specific details of how Ctf7, WAPL/Rad61, and Pds5 function together to first establish and then maintain cohesion still need to be clarified, recent results indicate that Ctf7 acetylates conserved Lys residues in SMC3, which inhibits the antiestablishment function of the Wpl1-Pds5 complex and promotes cohesion establishment (Ben-Shahar et al, 2008;Unal et al, 2008;Zhang et al, 2008;Rowland et al, 2009;Sutani et al, 2009). Ctf7 is also involved in the postreplicative induction of cohesion induced by DNA double-strand breaks (Unal et al, 2007).…”

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Proper Levels of the Arabidopsis Cohesion Establishment Factor CTF7 Are Essential for Embryo and Megagametophyte, But Not Endosperm, Development

Jiang

Xia

et al. 2010

Plant Physiology

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CTF7 is an essential gene in yeast that is required for the formation of sister chromatid cohesion. While recent studies have provided insights into how sister chromatid cohesion is established, less is known about how specifically CTF7 facilitates the formation of cohesion, and essentially nothing is known about how sister chromatid cohesion is established in plants. In this report, we describe the isolation and characterization of CTF7 from Arabidopsis (Arabidopsis thaliana). Arabidopsis CTF7 is similar to Saccharomyces cerevisiae CTF7 in that it lacks an amino-terminal extension, exhibits acetyltransferase activity, and can complement a yeast ctf7 temperature-sensitive mutation. CTF7 transcripts are found throughout the plant, with the highest levels present in buds. Seeds containing T-DNA insertions in CTF7 exhibit mitotic defects in the zygote. Interestingly, the endosperm developed normally in ctf7 seeds, suggesting that CTF7 is not essential for mitosis in endosperm nuclei. Minor defects were observed in female gametophytes of ctf7 1/2 plants, and plants that overexpress CTF7 exhibited female gametophyte lethality. Pollen development appeared normal in both CTF7 knockout and overexpression plants. Therefore, proper levels of CTF7 are critical for female gametophyte and embryo development but not for the establishment of mitotic cohesion during microgametogenesis or during endosperm development.The proper formation of sister chromatid cohesion and its subsequent release at the metaphase-to-anaphase transition is essential for the proper segregation of genetic material during cell division. It is critical for the compaction of chromosomes and their bipolar attachment to the spindle, DNA double-strand break repair, and the regulation of gene expression (for review, see Nasmyth and Haering, 2009). Sister chromatid cohesion is controlled by the cohesin complex, which consists of a heterodimer of Structural Maintenance of Chromosome (SMC) proteins, SMC1 and SMC3, Sister Chromatid Cohesion (SCC) protein SCC3, and SCC1, an a-kleisin protein. Perhaps the most widely accepted model of how cohesin functions has been referred to as the ring model, where the cohesin ring encircles the replicated sisters, holding them together until SCC1 cleavage by separase at the metaphase-to-anaphase transition opens the ring, allowing the release of the sister chromatids (for review, see Nasmyth and Haering, 2009).

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“…Loading of cohesin onto chromatin depends on two proteins, Scc2 and Scc4 (8,46). Once it is loaded onto chromatin, cohesin undergoes acetylation on Smc3 in S phase and establishes cohesion between the sister chromatids (34,43,50). In early mitosis in vertebrates, cohesin is removed from chromosomal arms following phosphorylation of the cohesin component SA2 (15, 45), leaving behind a small pool of cohesins at the centromeres.…”

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Calpain-1 Cleaves Rad21 To Promote Sister Chromatid Separation

Panigrahi

Zhang

Mao

et al. 2011

Molecular and Cellular Biology

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Defining the mechanisms of chromosomal cohesion and dissolution of the cohesin complex from chromatids is important for understanding the chromosomal missegregation seen in many tumor cells. Here we report the identification of a novel cohesin-resolving protease and describe its role in chromosomal segregation. Sister chromatids are held together by cohesin, a multiprotein ring-like complex comprised of Rad21, Smc1, Smc3, and SA2 (or SA1). Cohesin is known to be removed from vertebrate chromosomes by two distinct mechanisms, namely, the prophase and anaphase pathways. First, PLK1-mediated phosphorylation of SA2 in prophase leads to release of cohesin from chromosome arms, leaving behind centromeric cohesins that continue to hold the sisters together. Then, at the onset of anaphase, activated separase cleaves the centromeric cohesin Rad21, thereby opening the cohesin ring and allowing the sister chromatids to separate. We report here that the calcium-dependent cysteine endopeptidase calpain-1 is a Rad21 peptidase and normally localizes to the interphase nuclei and chromatin. Calpain-1 cleaves Rad21 at L192, in a calcium-dependent manner. We further show that Rad21 cleavage by calpain-1 promotes separation of chromosome arms, which coincides with a calcium-induced partial loss of cohesin at several chromosomal loci. Engineered cleavage of Rad21 at the calpain-cleavable site without activation of calpain-1 can lead to a loss of sister chromatid cohesion. Collectively, our work reveals a novel function of calpain-1 and describes an additional pathway for sister chromatid separation in humans.DNA replication in S phase generates two identical molecules of chromosomal DNA, known as sister chromatids, which must equally segregate to the two daughter cells in the subsequent mitosis. Therefore, it is important that the sister chromatids are held together from the S phase until proper kinetochore assembly is complete. Such cohesion of the sisters is mediated by a multiprotein ring-like complex called cohesin, which is conserved from Saccharomyces cerevisiae to humans. Cohesin is comprised of four core proteins, namely, Rad21 (Scc1/Mcd1), Smc1, Smc3, and either SA2/Stag2 or SA1/Stag1 (13,22,25,39; reviewed in reference 28). Cohesin undergoes a series of physical and chemical changes during the course of the cell cycle in order to orchestrate the dynamic cohesion and separation between the sister chromatids that are essential for high-fidelity transmission of the genetic material (32). The cohesin cycle includes loading cohesins onto the chromatin of the unpaired chromosome, forming cohesion between the sister chromatids in S phase, regulated freeing of chromosome arms in early mitosis, separation of sister chromatids to allow segregation to opposite poles, and recycling of cohesin molecules for subsequent usage.Cohesin is loaded onto the chromatin in G 1 phase in yeast (25) and in late telophase in vertebrates (21, 39). Loading of cohesin onto chromatin depends on two proteins, Scc2 and Scc4 (8,46). Once it is loaded onto...

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A Molecular Determinant for the Establishment of Sister Chromatid Cohesion

Cited by 436 publications

References 30 publications

Chromosome Dynamics during Mitosis

Chromosome Dynamics during Mitosis

Proper Levels of the Arabidopsis Cohesion Establishment Factor CTF7 Are Essential for Embryo and Megagametophyte, But Not Endosperm, Development

Calpain-1 Cleaves Rad21 To Promote Sister Chromatid Separation

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