Abstract
REC8 is a key component of the meiotic cohesin complex. During meiosis, cohesin is required for the establishment and maintenance of sister-chromatid cohesion, for the formation of the synaptonemal complex, and for recombination between homologous chromosomes. We show that REC8 has an essential role in mammalian meiosis, in that Rec8 null mice of both sexes have germ cell failure and are sterile. In the absence of REC8, early chromosome pairing events appear normal, but synapsis occurs in a novel fashion: between sister chromatids. This implies that a major role for REC8 in mammalian meiosis is to limit synapsis to between homologous chromosomes. In all other eukaryotic species studied to date, REC8 phenotypes have been restricted to meiosis. Unexpectedly, Rec8 null mice are born in sub-Mendelian frequencies and fail to thrive. These findings illuminate hitherto unknown REC8 functions in chromosome dynamics during mammalian meiosis and possibly in somatic development.
Publication types
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Comparative Study
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Research Support, Non-U.S. Gov't
MeSH terms
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Acetaminophen / analogs & derivatives*
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Acetaminophen / metabolism
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Animals
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Cell Cycle Proteins / metabolism
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Cell Death / physiology
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Chondroitin Sulfate Proteoglycans / metabolism
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Chromatids / metabolism*
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Chromatids / ultrastructure
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Chromosomal Proteins, Non-Histone / metabolism
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Chromosome Painting / methods
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Chromosome Pairing / physiology*
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Chromosomes / metabolism
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Chromosomes / ultrastructure
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Chromosomes, Human, Pair 10 / metabolism
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Cloning, Molecular / methods
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DNA-Binding Proteins / metabolism
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Electroporation / methods
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Female
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Humans
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Immunohistochemistry / methods
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In Situ Nick-End Labeling / methods
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Indoles / metabolism
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Male
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Meiosis / physiology*
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Meiotic Prophase I / physiology
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Mice
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Mice, Knockout
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Microscopy, Electron, Transmission / methods
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Models, Biological
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Nuclear Proteins / deficiency*
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Nuclear Proteins / genetics
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Nuclear Proteins / metabolism
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Nuclear Proteins / physiology*
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Oncorhynchus kisutch / metabolism
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Ovary / metabolism
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Pachytene Stage / physiology
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Phosphate-Binding Proteins
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Phosphoproteins / deficiency*
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Phosphoproteins / genetics
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Phosphoproteins / metabolism
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Phosphoproteins / physiology*
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Proliferating Cell Nuclear Antigen / metabolism
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Rad51 Recombinase
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Saccharin / analogs & derivatives*
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Saccharin / metabolism
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Spermatogenesis / genetics
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Testis / metabolism
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Testis / ultrastructure
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Trans-Activators / metabolism
Substances
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Cell Cycle Proteins
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Chondroitin Sulfate Proteoglycans
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Chromosomal Proteins, Non-Histone
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Cspg6 protein, mouse
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DNA-Binding Proteins
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Dmc1 protein, mouse
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Indoles
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Nuclear Proteins
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Phosphate-Binding Proteins
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Phosphoproteins
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Proliferating Cell Nuclear Antigen
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Rad21 protein, mouse
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Rec8 protein, mouse
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SCP 1
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Ss18l1 protein, rat
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Sycp3 protein, mouse
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Trans-Activators
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Acetaminophen
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DAPI
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RAD51 protein, human
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Rad51 Recombinase
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Rad51 protein, mouse
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DMC1 protein, human
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Saccharin