{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,2,27]],"date-time":"2026-02-27T01:39:28Z","timestamp":1772156368751,"version":"3.50.1"},"posted":{"date-parts":[[2023,9,26]]},"group-title":"Cell Biology","reference-count":68,"publisher":"openRxiv","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2023,12,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>\n                  Meiotic progression requires coordinated assembly and disassembly of protein complexes involved in chromosome synapsis and meiotic recombination. The AAA+ ATPase TRIP13 and its orthologue Pch2 are instrumental in remodeling HORMA domain proteins. Meiosis-specific HORMAD proteins are associated with unsynapsed chromosome axes but depleted from the synaptonemal complex (SC) of synapsed chromosome homologues. 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.\n                  <jats:italic>Trip13<\/jats:italic>\n                  -null meiocytes exhibit abnormal persistence of HORMAD1 and HOMRAD2 on synapsed SC and chromosome asynapsis that preferentially affects XY and centromeric ends. These findings confirm the previously reported phenotypes of the\n                  <jats:italic>Trip13<\/jats:italic>\n                  hypomorph alleles.\n                  <jats:italic>Trip13<\/jats:italic>\n                  heterozygous (\n                  <jats:italic>Trip13<\/jats:italic>\n                  <jats:sup>+\/-<\/jats:sup>\n                  ) mice also exhibit meiotic defects that are less severe than the\n                  <jats:italic>Trip13<\/jats:italic>\n                  -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. The N- or C-terminal FLAG-tagged TRIP13 proteins are functional and recapitulate the localization of native TRIP13 to SC and telomeres in knockin mice. Therefore, the evolutionarily conserved localization of TRIP13\/Pch2 to the synapsed chromosomes provides an explanation for dissociation of HORMA domain proteins upon chromosome synapsis in diverse organisms.\n                <\/jats:p>","DOI":"10.1101\/2023.09.25.559355","type":"posted-content","created":{"date-parts":[[2023,9,26]],"date-time":"2023-09-26T11:35:14Z","timestamp":1695728114000},"source":"Crossref","is-referenced-by-count":4,"title":["TRIP13 localizes to synapsed chromosomes and functions as a dosage-sensitive regulator of meiosis"],"prefix":"10.64898","author":[{"given":"Jessica Y.","family":"Chotiner","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"N. Adrian","family":"Leu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fang","family":"Yang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Isabella G.","family":"Cossu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yongjuan","family":"Guan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Huijuan","family":"Lin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2311-4089","authenticated-orcid":false,"given":"P. Jeremy","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"54368","reference":[{"key":"2023121923550582000_2023.09.25.559355v2.1","doi-asserted-by":"crossref","first-page":"4113","DOI":"10.1016\/j.cub.2020.07.089","article-title":"COMET Functions as a PCH2 Cofactor in Regulating the HORMA Domain Protein ASY1","volume":"30","year":"2020","journal-title":"Curr Biol"},{"key":"2023121923550582000_2023.09.25.559355v2.2","doi-asserted-by":"crossref","first-page":"e1002701","DOI":"10.1371\/journal.pgen.1002701","article-title":"Synaptonemal complex components persist at centromeres and are required for homologous centromere pairing in mouse spermatocytes","volume":"8","year":"2012","journal-title":"PLoS 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