Eco1 Is a Novel Acetyltransferase that Can Acetylate Proteins Involved in Cohesion

Research Institute of Molecular Pathology, Dr. Bohr-Gasse 7, A-1030, Vienna, Austria.
Current Biology (Impact Factor: 9.57). 03/2002; 12(4):323-8. DOI: 10.1016/S0960-9822(02)00681-4
Source: PubMed


Cohesion between sister chromatids is established during S phase and maintained through G2 phase until it is resolved in anaphase (for review, see [1-3]). In Saccharomyces cerevisiae, a complex consisting of Scc1, Smc1, Smc3, and Scc3 proteins, called "cohesin," mediates the connection between sister chromatids. The evolutionary conserved yeast protein Eco1 is required for establishment of sister chromatid cohesion during S phase but not for its further maintenance during G2 or M phases or for loading the cohesin complex onto DNA. We address the molecular functions of Eco1 with sensitive sequence analytic techniques, including hidden Markov model domain fragment searches. We found a two-domain architecture with an N-terminal C2H2 Zn finger-like domain and an approximately 150 residue C-terminal domain with an apparent acetyl coenzyme A binding motif ( Biochemical tests confirm that Eco1 has the acetyltransferase activity in vitro. In vitro Eco1 acetylates itself and components of the cohesin complex but not histones. Thus, the establishment of cohesion between sister chromatids appears to be regulated, directly or indirectly, by a specific acetyltransferase.

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    • "Mutations in ESCO2 lead to Roberts syndrome (RBS), which is associated with a variety of defects including growth retardation, limb reduction/asymmetric limb growth, cleft lip/palate and missing fingers/toes[26,27]the framework of the acetyltransferase domain. Motif A participates in acetyl-CoA binding and is critical for catalytic activity, while motif B is the most Cterminal region and participates in substrate recognition and catalytic activity regulation[28,29]. Variations in AtCTF7 expression have been shown to result in a wide range of defects . "
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    ABSTRACT: Eco1/Ctf7 is essential for the establishment of sister chromatid cohesion during S phase of the cell cycle. Inactivation of Ctf7/Eco1 leads to a lethal phenotype in most organisms. Altering Eco1/Ctf7 levels or point mutations in the gene can lead to alterations in nuclear division as well as a wide range of developmental defects. Inactivation of Arabidopsis CTF7 (AtCTF7) results in severe defects in reproduction and vegetative growth. To further investigate the function(s) of AtCTF7, a tagged version of AtCTF7 and several AtCTF7 deletion constructs were created and transformed into wild type or ctf7 (+/-) plants. Transgenic plants expressing 35S:NTAP:AtCTF7∆299-345 (AtCTF7∆B) displayed a wide range of phenotypic alterations in reproduction and vegetative growth. Male meiocytes exhibited chromosome fragmentation and uneven chromosome segregation. Mutant ovules contained abnormal megasporocyte-like cells during pre-meiosis, megaspores experienced elongated meiosis and megagametogenesis, and defective megaspores/embryo sacs were produced at various stages. The transgenic plants also exhibited a broad range of vegetative defects, including meristem disruption and dwarfism that were inherited in a non-Mendelian fashion. Transcripts for epigenetically regulated transposable elements (TEs) were elevated in transgenic plants. Transgenic plants expressing 35S:AtCTF7∆B displayed similar vegetative defects, suggesting the defects in 35S:NTAP:AtCTF7∆B plants are caused by high-level expression of AtCTF7∆B. High level expression of AtCTF7∆B disrupts megasporogenesis, megagametogenesis and male meiosis, as well as causing a broad range of vegetative defects, including dwarfism that are inherited in a non-Mendelian fashion.
    Full-text · Article · Dec 2015 · BMC Plant Biology
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    • "These two proteins are conserved from yeast to human. An acetyltransferase called Eco1 (known in mammalian cells as Esco1 and Esco2), which acetylates Smc3, is crucial for cohesin establishment (Ivanov et al., 2002). Smc3 acetylation is reversed at anaphase by the Hos1 deacetylatase as a consequence of Scc1 cleavage (Beckouët et al., 2010;Xiong et al., 2010). "
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    ABSTRACT: Chromosome segregation is a tightly regulated process through which duplicated genetic materials are equally partitioned into daughter cells. During the past decades, tremendous efforts have been made to understand the molecular mechanism of chromosome segregation using animals and yeasts as model systems. Recently, new insights into chromosome segregation have gradually emerged using trypanosome, an early branching parasitic protozoan, as a model organism. To uncover the unique aspects of chromosome segregation in trypanosome, which potentially could serve as new drug targets for anti-trypanosome chemotherapy, it is necessary to perform a comparative analysis of the chromosome segregation machinery between trypanosome and its human host. Here, we briefly review the current knowledge about chromosome segregation in human and Trypanosoma brucei, with a focus on the regulation of cohesin and securin degradation triggered by the activation of the anaphase promoting complex/cyclosome (APC/C). We also include yeasts in our comparative analysis since some of the original discoveries were made using budding and fission yeasts as the model organisms and, therefore, these could provide hints about the evolution of the machinery. We highlight both common and unique features in these model systems and also provide perspectives for future research in trypanosome.
    Full-text · Article · Dec 2014
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    • "Cohesin is deposited across chromosomes by the SCC2/4 cohesin loader. Cohesin becomes cohesive during DNA replication through acetylation by Eco1 (Ivanov et al. 2002; Rolef Ben-Shahar et al. 2008; Unal et al. 2008; Zhang et al. 2008; Heidinger-Pauli et al. 2009). Activation of cohesin is linked to DNA replication via proteins like Ctf4 and Ctf8 (Lengronne et al. 2006; Skibbens 2009) that facilitate the acetylation of cohesin. "
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    Preview · Article · Dec 2013 · Genetics
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