Article

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

ABSTRACT

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 (http://mendel.imp.univie.ac.at/SEQUENCES/ECO1/). 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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    • "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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    • "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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