title: Cohesin Releases DNA through Asymmetric ATPase-Driven Ring Opening.
abstract: Cohesin stably holds together the sister chromatids from S phase until mitosis. To do so, cohesin must be protected against its cellular antagonist Wapl. Eco1 acetylates cohesin's Smc3 subunit, which locks together the sister DNAs. We used yeast genetics to dissect how Wapl drives cohesin from chromatin and identified mutants of cohesin that are impaired in ATPase activity but remarkably confer robust cohesion that bypasses the need for the cohesin protectors Eco1 in yeast and Sororin in human cells. We uncover a functional asymmetry within the heart of cohesin's highly conserved ABC-like ATPase machinery and find that both ATPase sites contribute to DNA loading, whereas DNA release is controlled specifically by one site. We propose that Smc3 acetylation locks cohesin rings around the sister chromatids by counteracting an activity associated with one of cohesin's two ATPase sites.
authors.affiliation: Division of Cell Biology, The Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands.
authors.forename: Ahmed M O
authors.initials: AMO
authors.lastname: Elbatsh
authors.affiliation: Division of Cell Biology, The Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands.
authors.forename: Judith H I
authors.initials: JHI
authors.lastname: Haarhuis
authors.affiliation: Department of Biochemistry, University of Oxford, South Parks Road, OX1 3QU, Oxford, United Kingdom.
authors.forename: Naomi
authors.initials: N
authors.lastname: Petela
authors.affiliation: Department of Biochemistry, University of Oxford, South Parks Road, OX1 3QU, Oxford, United Kingdom.
authors.forename: Christophe
authors.initials: C
authors.lastname: Chapard
authors.affiliation: Division of Biochemistry, The Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands.
authors.forename: Alexander
authors.initials: A
authors.lastname: Fish
authors.affiliation: Division of Biochemistry, The Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands.
authors.forename: Patrick H
authors.initials: PH
authors.lastname: Celie
authors.affiliation: Division of Biochemistry, The Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands.
authors.forename: Magda
authors.initials: M
authors.lastname: Stadnik
authors.affiliation: Department of Genetics, Cancer Genomics Netherlands, and Department of Radiation Oncology, Erasmus University Medical Center, 3000 CA Rotterdam, The Netherlands.
authors.forename: Dejan
authors.initials: D
authors.lastname: Ristic
authors.affiliation: Department of Genetics, Cancer Genomics Netherlands, and Department of Radiation Oncology, Erasmus University Medical Center, 3000 CA Rotterdam, The Netherlands.
authors.forename: Claire
authors.initials: C
authors.lastname: Wyman
authors.affiliation: Division of Cell Biology, The Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands.
authors.forename: René H
authors.initials: RH
authors.lastname: Medema
authors.affiliation: Department of Biochemistry, University of Oxford, South Parks Road, OX1 3QU, Oxford, United Kingdom.
authors.forename: Kim
authors.initials: K
authors.lastname: Nasmyth
authors.affiliation: Division of Cell Biology, The Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands. Electronic address: b.rowland@nki.nl.
authors.forename: Benjamin D
authors.initials: BD
authors.lastname: Rowland
mesh_terms: D000107:Acetylation; D000251:Adenosine Triphosphatases / Q000378:metabolism*; D020134:Catalytic Domain; D002453:Cell Cycle; D018797:Cell Cycle Proteins / Q000378:metabolism*; D002843:Chromatin / Q000235:genetics; D002868:Chromosomal Proteins, Non-Histone / Q000378:metabolism*; D004247:DNA / Q000378:metabolism*; D006801:Humans; D009687:Nuclear Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D012441:Saccharomyces cerevisiae / Q000235:genetics* / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D000097722:Cohesins
chemical_list: D000251:Adenosine Triphosphatases; D018797:Cell Cycle Proteins; D002843:Chromatin; D002868:Chromosomal Proteins, Non-Histone; D004247:DNA; D009687:Nuclear Proteins; D029701:Saccharomyces cerevisiae Proteins; D000097722:Cohesins