title: Genetic evidence that the acetylation of the Smc3p subunit of cohesin modulates its ATP-bound state to promote cohesion establishment in Saccharomyces cerevisiae.
abstract: Sister chromatid cohesion refers to the process by which sister chromatids are tethered together until the metaphase-to-anaphase transition. The evolutionarily conserved cohesin complex mediates sister chromatid cohesion. Cohesin not only ensures proper chromosome segregation, but also promotes high-fidelity DNA repair and transcriptional regulation. Two subunits of cohesin (Smc1p, Smc3p) are members of the structural maintenance of chromosomes (SMC) family. The SMC family is recognized by their large coiled-coil arms and conserved ATP-binding cassette-like ATPase domain. While both Smc1p and Smc3p ATP binding and hydrolysis are essential for cohesin function in vivo, little is known about how this core enzymatic activity is regulated to facilitate sister chromatid cohesion. Here we use SMC mutant proteins to block specific steps in cohesin's ATPase cycle in Saccharomyces cerevisiae. We show that blocking Smc3p-mediated ATP binding or Smc3p ATP hydrolysis traps unique functional states in cohesion. Finally, we provide evidence that Smc3p acetylation, which has an essential role in cohesion establishment, modulates the Smc3p ATP-bound state.
authors.affiliation: Howard Hughes Medical Institute, Department of Embryology, Carnegie Institution, Baltimore, Maryland 21218, USA.
authors.forename: Jill M
authors.initials: JM
authors.lastname: Heidinger-Pauli
authors.forename: Itay
authors.initials: I
authors.lastname: Onn
authors.forename: Douglas
authors.initials: D
authors.lastname: Koshland
mesh_terms: D000107:Acetylation; D000251:Adenosine Triphosphatases / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000378:metabolism*; D015153:Blotting, Western; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism*; D002842:Chromatids / Q000235:genetics; D047369:Chromatin Immunoprecipitation; D002868:Chromosomal Proteins, Non-Histone / Q000235:genetics / Q000378:metabolism*; D020090:Chromosome Segregation; D015825:Chromosomes, Fungal / Q000235:genetics; D016193:G1 Phase; D006868:Hydrolysis; D009154:Mutation; D011485:Protein Binding; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D018797:Cell Cycle Proteins; D002868:Chromosomal Proteins, Non-Histone; C120372:SMC3 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D000255:Adenosine Triphosphate; D000251:Adenosine Triphosphatases