2. Academic Validation
  3. Sister Chromatid Cohesion Establishment Factor ESCO1 Operates by Substrate-Assisted Catalysis

Sister Chromatid Cohesion Establishment Factor ESCO1 Operates by Substrate-Assisted Catalysis

  • Structure. 2016 May 3;24(5):789-796. doi: 10.1016/j.str.2016.03.021.
Ekaterina Kouznetsova 1,  Takaharu Kanno 2,  Tobias Karlberg 1,  Ann-Gerd Thorsell 1,  Magdalena Wisniewska 1,  Petri Kursula 3,  Camilla Sjögren 2,  Herwig Schüler 4
Affiliations

Affiliations

  • 1 Structural Genomics Consortium and Department of Medical Biochemistry and Biophysics, Karolinska Institutet, 17177 Stockholm, Sweden.
  • 2 Department of Cellular and Molecular Biology, Karolinska Institutet, 17177 Stockholm, Sweden.
  • 3 Department of Biomedicine, University of Bergen, 5020 Bergen, Norway; Faculty of Biochemistry and Molecular Medicine, Biocenter Oulu, University of Oulu, 90014 Oulu, Finland.
  • 4 Structural Genomics Consortium and Department of Medical Biochemistry and Biophysics, Karolinska Institutet, 17177 Stockholm, Sweden. Electronic address: [email protected].
PMID: 27112597 DOI: 10.1016/j.str.2016.03.021
Abstract

Sister chromatid cohesion, formed by the cohesin protein complex, is essential for chromosome segregation. In order for cohesion to be established, the cohesin subunit SMC3 needs to be acetylated by a homolog of the ESCO1/Eco1 acetyltransferases, the enzymatic mechanism of which has remained unknown. Here we report the crystal structure of the ESCO1 acetyltransferase domain in complex with acetyl-coenzyme A, and show by SAXS that ESCO1 is a dimer in solution. The structure reveals an active site that lacks a potential catalytic base side chain. However, mutation of glutamate 789, a surface residue that is close to the automodification target lysine 803, strongly reduces autoacetylation of ESCO1. Moreover, budding yeast Smc3 mutated at the conserved residue D114, adjacent to the cohesion-activating acetylation site K112,K113, cannot be acetylated in vivo. This indicates that ESCO1 controls cohesion through substrate-assisted catalysis. Thus, this study discloses a key mechanism for cohesion establishment.

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