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TRIP13 localizes to synapsed chromosomes and functions as a dosage-sensitive regulator of meiosis

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  • معلومة اضافية
    • بيانات النشر:
      eLife Sciences Publications Ltd, 2024.
    • الموضوع:
      2024
    • Collection:
      LCC:Medicine
      LCC:Science
      LCC:Biology (General)
    • نبذة مختصرة :
      Meiotic progression requires coordinated assembly and disassembly of protein complexes involved in chromosome synapsis and meiotic recombination. Mouse TRIP13 and its ortholog Pch2 are instrumental in remodeling HORMA domain proteins. HORMAD proteins are associated with unsynapsed chromosome axes but depleted from the synaptonemal complex (SC) of synapsed homologs. Here we report that TRIP13 localizes to the synapsed SC in early pachytene spermatocytes and to telomeres throughout meiotic prophase I. Loss of TRIP13 leads to meiotic arrest and thus sterility in both sexes. Trip13-null meiocytes exhibit abnormal persistence of HORMAD1 and HOMRAD2 on synapsed SC and chromosome asynapsis that preferentially affects XY and centromeric ends. These major phenotypes are consistent with reported phenotypes of Trip13 hypomorph alleles. Trip13 heterozygous mice exhibit meiotic defects that are less severe than the Trip13-null mice, showing that TRIP13 is a dosage-sensitive regulator of meiosis. Localization of TRIP13 to the synapsed SC is independent of SC axial element proteins such as REC8 and SYCP2/SYCP3. Terminal FLAG-tagged TRIP13 proteins are functional and recapitulate the localization of native TRIP13 to SC and telomeres. Therefore, the evolutionarily conserved localization of TRIP13/Pch2 to the synapsed chromosomes provides an explanation for dissociation of HORMA domain proteins upon synapsis in diverse organisms.
    • File Description:
      electronic resource
    • ISSN:
      2050-084X
    • Relation:
      https://elifesciences.org/articles/92195; https://doaj.org/toc/2050-084X
    • الرقم المعرف:
      10.7554/eLife.92195
    • الرقم المعرف:
      edsdoj.0256f45fcbe84407aa849f5a310cbbd1