title: MAJIN Links Telomeric DNA to the Nuclear Membrane by Exchanging Telomere Cap.
abstract: In meiosis, telomeres attach to the inner nuclear membrane (INM) and drive the chromosome movement required for homolog pairing and recombination. Here, we address the question of how telomeres are structurally adapted for the meiotic task. We identify a multi-subunit meiotic telomere-complex, TERB1/2-MAJIN, which takes over telomeric DNA from the shelterin complex in mouse germ cells. TERB1/2-MAJIN initially assembles on the INM sequestered by its putative transmembrane subunit MAJIN. In early meiosis, telomere attachment is achieved by the formation of a chimeric complex of TERB1/2-MAJIN and shelterin. The chimeric complex matures during prophase into DNA-bound TERB1/2-MAJIN by releasing shelterin, forming a direct link between telomeric DNA and the INM. These hierarchical processes, termed "telomere cap exchange," are regulated by CDK-dependent phosphorylation and the DNA-binding activity of MAJIN. Further, we uncover a positive feedback between telomere attachment and chromosome movement, revealing a comprehensive regulatory network underlying meiosis-specific telomere function in mammals.
authors.affiliation: Laboratory of Chromosome Dynamics, Institute of Molecular and Cellular Biosciences, University of Tokyo, 1-1-1Yayoi, Tokyo 113-0032, Japan.
authors.forename: Hiroki
authors.initials: H
authors.lastname: Shibuya
authors.affiliation: Department of Cell and Molecular Biology, Karolinska Institute, Stockholm 171 77, Sweden.
authors.forename: Abrahan
authors.initials: A
authors.lastname: Hernández-Hernández
authors.affiliation: Laboratory of Chromosome Dynamics, Institute of Molecular and Cellular Biosciences, University of Tokyo, 1-1-1Yayoi, Tokyo 113-0032, Japan.
authors.forename: Akihiro
authors.initials: A
authors.lastname: Morimoto
authors.affiliation: Laboratory of Protein Expression and Production, Center for Structural Biology of Challenging Proteins, Institute of Molecular and Cellular Biosciences, University of Tokyo, 1-1-1 Yayoi, Tokyo 113-0032, Japan.
authors.forename: Lumi
authors.initials: L
authors.lastname: Negishi
authors.affiliation: Department of Cell and Molecular Biology, Karolinska Institute, Stockholm 171 77, Sweden.
authors.forename: Christer
authors.initials: C
authors.lastname: Höög
authors.affiliation: Laboratory of Chromosome Dynamics, Institute of Molecular and Cellular Biosciences, University of Tokyo, 1-1-1Yayoi, Tokyo 113-0032, Japan. Electronic address: ywatanab@iam.u-tokyo.ac.jp.
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Watanabe
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D051017:Apoptosis Regulatory Proteins / Q000737:chemistry / Q000378:metabolism; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008297:Male; D008540:Meiosis; D008565:Membrane Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D008869:Microtubule-Associated Proteins / Q000235:genetics; D008969:Molecular Sequence Data; D009685:Nuclear Envelope / Q000378:metabolism*; D009687:Nuclear Proteins / Q000737:chemistry / Q000378:metabolism; D016415:Sequence Alignment; D016615:Telomere / Q000378:metabolism*; D034501:Telomere-Binding Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D013737:Testis / Q000378:metabolism; D009218:Myosins
chemical_list: D051017:Apoptosis Regulatory Proteins; D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D008565:Membrane Proteins; D008869:Microtubule-Associated Proteins; D009687:Nuclear Proteins; D034501:Telomere-Binding Proteins; C000606103:MAJIN protein, mouse; C464932:SUN1 protein, mouse; C587999:TERB1 protein, mouse; C000606104:TERB2 protein, mouse; C407152:MYO18A protein, human; D009218:Myosins