title: SMC5/6 is required for the formation of segregation-competent bivalent chromosomes during meiosis I in mouse oocytes.
abstract: SMC complexes include three major classes: cohesin, condensin and SMC5/6. However, the localization pattern and genetic requirements for the SMC5/6 complex during mammalian oogenesis have not previously been examined. In mouse oocytes, the SMC5/6 complex is enriched at the pericentromeric heterochromatin, and also localizes along chromosome arms during meiosis. The infertility phenotypes of females with aZp3-Cre-driven conditional knockout (cKO) ofSmc5demonstrated that maternally expressed SMC5 protein is essential for early embryogenesis. Interestingly, protein levels of SMC5/6 complex components in oocytes decline as wild-type females age. When SMC5/6 complexes were completely absent in oocytes during meiotic resumption, homologous chromosomes failed to segregate accurately during meiosis I. Despite what appears to be an inability to resolve concatenation between chromosomes during meiosis, localization of topoisomerase IIα to bivalents was not affected; however, localization of condensin along the chromosome axes was perturbed. Taken together, these data demonstrate that the SMC5/6 complex is essential for the formation of segregation-competent bivalents during meiosis I, and findings suggest that age-dependent depletion of the SMC5/6 complex in oocytes could contribute to increased incidence of oocyte aneuploidy and spontaneous abortion in aging females.
authors.affiliation: Department of Biochemistry and Molecular Biology, Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD 21205, USA.
authors.forename: Grace
authors.initials: G
authors.lastname: Hwang
authors.affiliation: The Jackson Laboratory, Bar Harbor, ME 04609, USA.
authors.forename: Fengyun
authors.initials: F
authors.lastname: Sun
authors.affiliation: The Jackson Laboratory, Bar Harbor, ME 04609, USA.
authors.forename: Marilyn
authors.identifier: 0000-0001-6634-0815
authors.initials: M
authors.lastname: O'Brien
authors.affiliation: The Jackson Laboratory, Bar Harbor, ME 04609, USA.
authors.forename: John J
authors.initials: JJ
authors.lastname: Eppig
authors.affiliation: The Jackson Laboratory, Bar Harbor, ME 04609, USA.
authors.forename: Mary Ann
authors.initials: MA
authors.lastname: Handel
authors.affiliation: Department of Biochemistry and Molecular Biology, Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD 21205, USA pjordan8@jhu.edu.|The Jackson Laboratory, Bar Harbor, ME 04609, USA.
authors.forename: Philip W
authors.identifier: 0000-0003-4890-2647
authors.initials: PW
authors.lastname: Jordan
mesh_terms: D000251:Adenosine Triphosphatases / Q000378:metabolism; D000375:Aging / Q000502:physiology; D000782:Aneuploidy; D000818:Animals; D001755:Blastocyst / Q000166:cytology / Q000378:metabolism; D018797:Cell Cycle Proteins / Q000378:metabolism*; D020090:Chromosome Segregation; D033481:Chromosomes, Mammalian / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000378:metabolism; D005260:Female; D005307:Fertilization in Vitro; D060005:Genotyping Techniques; D006570:Heterochromatin / Q000378:metabolism; D007247:Infertility, Female; D019426:Integrases / Q000378:metabolism; D008297:Male; D000072741:Maternal Inheritance / Q000235:genetics; D008540:Meiosis; D008677:Metaphase; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008954:Models, Biological; D046912:Multiprotein Complexes / Q000378:metabolism; D009154:Mutation / Q000235:genetics; D009865:Oocytes / Q000166:cytology* / Q000378:metabolism*; D012726:Sexual Behavior, Animal
chemical_list: D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D006570:Heterochromatin; D046912:Multiprotein Complexes; C000613261:SMC5 protein, mouse; C583968:SMC6 protein, mouse; C108312:condensin complexes; C045073:Cre recombinase; D019426:Integrases; D000251:Adenosine Triphosphatases
keywords: Aneuploidy; Chromosome segregation; Cohesin; Condensin; Meiosis; SMC5/6