title: Chromosome Cohesion Established by Rec8-Cohesin in Fetal Oocytes Is Maintained without Detectable Turnover in Oocytes Arrested for Months in Mice.
abstract: Sister chromatid cohesion mediated by the cohesin complex is essential for chromosome segregation in mitosis and meiosis [1]. Rec8-containing cohesin, bound to Smc3/Smc1α or Smc3/Smc1β, maintains bivalent cohesion in mammalian meiosis [2-6]. In females, meiotic DNA replication and recombination occur in fetal oocytes. After birth, oocytes arrest at the prolonged dictyate stage until recruited to grow into mature oocytes that divide at ovulation. How cohesion is maintained in arrested oocytes remains a pivotal question relevant to maternal age-related aneuploidy. Hypothetically, cohesin turnover regenerates cohesion in oocytes. Evidence for post-replicative cohesion establishment mechanism exists, in yeast and invertebrates [7, 8]. In mouse fetal oocytes, cohesin loading factor Nipbl/Scc2 localizes to chromosome axes during recombination [9, 10]. Alternatively, cohesion is maintained without turnover. Consistent with this, cohesion maintenance does not require Smc1β transcription, but unlike Rec8, Smc1β is not required for establishing bivalent cohesion [11, 12]. Rec8 maintains cohesion without turnover during weeks of oocyte growth [3]. Whether the same applies to months or decades of arrest is unknown. Here, we test whether Rec8 activated in arrested mouse oocytes builds cohesion revealed by TEV cleavage and live-cell imaging. Rec8 establishes cohesion when activated during DNA replication in fetal oocytes using tamoxifen-inducible Cre. In contrast, no new cohesion is detected when Rec8 is activated in arrested oocytes by tamoxifen despite cohesin synthesis. We conclude that cohesion established in fetal oocytes is maintained for months without detectable turnover in dictyate-arrested oocytes. This implies that women's fertility depends on the longevity of cohesin proteins that established cohesion in utero.
authors.affiliation: Institute of Molecular Biotechnology of the Austrian Academy of Sciences (IMBA), Vienna Biocenter Campus, Dr. Bohr-Gasse 3, Vienna 1030, Austria.
authors.forename: Sabrina
authors.initials: S
authors.lastname: Burkhardt
authors.affiliation: Institute of Molecular Biotechnology of the Austrian Academy of Sciences (IMBA), Vienna Biocenter Campus, Dr. Bohr-Gasse 3, Vienna 1030, Austria.
authors.forename: Máté
authors.initials: M
authors.lastname: Borsos
authors.affiliation: Institute of Molecular Biotechnology of the Austrian Academy of Sciences (IMBA), Vienna Biocenter Campus, Dr. Bohr-Gasse 3, Vienna 1030, Austria.
authors.forename: Anna
authors.initials: A
authors.lastname: Szydlowska
authors.affiliation: Department of Biochemistry, University of Oxford, South Parks Road, Oxford OX1 3QU, UK.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Godwin
authors.affiliation: Nuffield Department of Obstetrics and Gynaecology, John Radcliffe Hospital, University of Oxford, Women's Centre, Level 3, Oxford OX3 9DU, UK.
authors.forename: Suzannah A
authors.initials: SA
authors.lastname: Williams
authors.affiliation: Department of Biomedical Sciences and Center for Reproductive Genomics, Cornell University, Tower Road, Ithaca, NY 14853, USA.
authors.forename: Paula E
authors.initials: PE
authors.lastname: Cohen
authors.affiliation: Department of Anatomy and Cell Biology, Graduate School of Medicine, Kyoto University, Yoshida-Konoe-cho, Sakyo-ku, Kyoto 606-8501, Japan; JST, ERATO, Yoshida-Konoe-cho, Sakyo-ku, Kyoto 606-8501, Japan.
authors.forename: Takayuki
authors.initials: T
authors.lastname: Hirota
authors.affiliation: Department of Anatomy and Cell Biology, Graduate School of Medicine, Kyoto University, Yoshida-Konoe-cho, Sakyo-ku, Kyoto 606-8501, Japan; JST, ERATO, Yoshida-Konoe-cho, Sakyo-ku, Kyoto 606-8501, Japan.
authors.forename: Mitinori
authors.initials: M
authors.lastname: Saitou
authors.affiliation: Institute of Molecular Biotechnology of the Austrian Academy of Sciences (IMBA), Vienna Biocenter Campus, Dr. Bohr-Gasse 3, Vienna 1030, Austria. Electronic address: kikue.tachibana@imba.oeaw.ac.at.
authors.forename: Kikuë
authors.initials: K
authors.lastname: Tachibana-Konwalski
mesh_terms: D000818:Animals; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism; D002868:Chromosomal Proteins, Non-Histone / Q000235:genetics / Q000378:metabolism; D020090:Chromosome Segregation; D005260:Female; D051379:Mice; D009687:Nuclear Proteins / Q000235:genetics* / Q000378:metabolism; D009865:Oocytes / Q000378:metabolism*; D010750:Phosphoproteins / Q000235:genetics* / Q000378:metabolism; D000097722:Cohesins
chemical_list: D018797:Cell Cycle Proteins; D002868:Chromosomal Proteins, Non-Histone; D009687:Nuclear Proteins; D010750:Phosphoproteins; D000097722:Cohesins; C465863:Rec8 protein, mouse
keywords: cohesin; meiosis; oocytes