title: Sororin actively maintains sister chromatid cohesion.
abstract: Cohesion between sister chromatids is established during DNA replication but needs to be maintained to enable proper chromosome-spindle attachments in mitosis or meiosis. Cohesion is mediated by cohesin, but also depends on cohesin acetylation and sororin. Sororin contributes to cohesion by stabilizing cohesin on DNA. Sororin achieves this by inhibiting WAPL, which otherwise releases cohesin from DNA and destroys cohesion. Here we describe mouse models which enable the controlled depletion of sororin by gene deletion or auxin-induced degradation. We show that sororin is essential for embryonic development, cohesion maintenance, and proper chromosome segregation. We further show that the acetyltransferases ESCO1 and ESCO2 are essential for stabilizing cohesin on chromatin, that their only function in this process is to acetylate cohesin's SMC3 subunit, and that DNA replication is also required for stable cohesin-chromatin interactions. Unexpectedly, we find that sororin interacts dynamically with the cohesin complexes it stabilizes. This implies that sororin recruitment to cohesin does not depend on the DNA replication machinery or process itself, but on a property that cohesin acquires during cohesion establishment.
authors.affiliation: IMP Research Institute of Molecular Pathology, Vienna, Austria.
authors.forename: Rene
authors.initials: R
authors.lastname: Ladurner
authors.affiliation: IMP Research Institute of Molecular Pathology, Vienna, Austria.
authors.forename: Emanuel
authors.initials: E
authors.lastname: Kreidl
authors.affiliation: IMP Research Institute of Molecular Pathology, Vienna, Austria.
authors.forename: Miroslav P
authors.initials: MP
authors.lastname: Ivanov
authors.affiliation: Campus Science Support Facilities NGS Facility, Vienna, Austria.
authors.forename: Heinz
authors.initials: H
authors.lastname: Ekker
authors.affiliation: IMP Research Institute of Molecular Pathology, Vienna, Austria.
authors.forename: Maria Helena
authors.initials: MH
authors.lastname: Idarraga-Amado
authors.affiliation: IMP Research Institute of Molecular Pathology, Vienna, Austria.
authors.forename: Georg A
authors.initials: GA
authors.lastname: Busslinger
authors.affiliation: IMP Research Institute of Molecular Pathology, Vienna, Austria.
authors.forename: Gordana
authors.initials: G
authors.lastname: Wutz
authors.affiliation: IMP Research Institute of Molecular Pathology, Vienna, Austria.
authors.forename: David A
authors.initials: DA
authors.lastname: Cisneros
authors.affiliation: IMP Research Institute of Molecular Pathology, Vienna, Austria Jan-Michael.Peters@imp.ac.at.
authors.forename: Jan-Michael
authors.initials: JM
authors.lastname: Peters
mesh_terms: D000123:Acetyltransferases / Q000378:metabolism; D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism*; D002842:Chromatids / Q000378:metabolism*; D020090:Chromosome Segregation; D047108:Embryonic Development; D051379:Mice
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C500696:Cdca5 protein, mouse; D018797:Cell Cycle Proteins; D000123:Acetyltransferases; C000609285:ESCO1 protein, mouse; C568919:establishment of cohesion 1 homolog 2, mouse
keywords: cell cycle; cohesin acetylation; mitosis; sister chromatid cohesion