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In mice, shortage in chiasmata 1 (SHOC1) forms a trimeric complex with the other two ZMM proteins, SPO16 and TEX11, to bind recombination intermediates after strand invasion. Although genetic variants of SHOC1 are clinically associated with male infertility, their conserved functions in human gametogenesis remain enigmatic. Here, we delineated species-specific divergences between human and mouse SHOC1 complex and identified a missense variant within the XPF-like domain in SHOC1 (p.Q590R). This variant impaired DNA double-strand breaks repair by compromising its ability to bind branched DNA structures and the recruitment of crucial proteins to recombination intermediates, ultimately abolishing CO formation. Furthermore, the variant disrupted dynamic chromatin structure in pachytene spermatocytes and induced synapsis defects. Importantly, the XPF-like domain in SHOC1 was revealed to prevent autosome intrusion into the sex body compartment, thereby protecting critical autosomal loci from meiotic silencing of unsynapsed chromatin (MSUC). Overall, our study underscores the critical role of the XPF-like domain in human SHOC1 in CO formation and in protecting autosomes from MSUC.<\/jats:p>","DOI":"10.1093\/nar\/gkag558","type":"journal-article","created":{"date-parts":[[2026,5,22]],"date-time":"2026-05-22T11:52:40Z","timestamp":1779450760000},"source":"Crossref","is-referenced-by-count":1,"title":["XPF-like domain in human SHOC1 is required for crossover formation and protecting autosome from MSUC"],"prefix":"10.1093","volume":"54","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3176-7146","authenticated-orcid":false,"given":"Yuxiang","family":"Zhang","sequence":"first","affiliation":[{"name":"Department of Andrology, Center for Men\u2019s Health, Department of ART, Institute of Urology, Urologic Medical Center, Shanghai Key Laboratory of Reproductive Medicine, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine , Shanghai 200080 ,","place":["China"]},{"name":"Department of Developmental and Regenerative Biology,\u00a0School of Life Science and Technology, ShanghaiTech University , Shanghai 200120 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qian","family":"Sun","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Reproductive Medicine and Offspring Health, Nanjing Medical University , Nanjing 211166 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhiyong","family":"Ji","sequence":"additional","affiliation":[{"name":"Department of Reproductive Medicine, The First Affiliated Hospital of Xiamen University, School of Medicine, Xiamen University , Xiamen 361003 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ren","family":"Mo","sequence":"additional","affiliation":[{"name":"Department of Urology, Inner Mongolia People\u2019s Hospital, Inner Mongolia Urological Institute , Hohhot, Inner Mongolia 010017 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9501-5568","authenticated-orcid":false,"given":"Yuchuan","family":"Zhou","sequence":"additional","affiliation":[{"name":"The International Peace Maternity and Child Health Hospital, Shanghai Key Laboratory of Embryo Original Disease, School of Medicine, Shanghai Jiao Tong University , Shanghai 200030 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingpeng","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Andrology, Center for Men\u2019s Health, Department of ART, Institute of Urology, Urologic Medical Center, Shanghai Key Laboratory of Reproductive Medicine, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine , Shanghai 200080 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuai","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Andrology, Center for Men\u2019s Health, Department of ART, Institute of Urology, Urologic Medical Center, Shanghai Key Laboratory of Reproductive Medicine, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine , Shanghai 200080 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Na","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Andrology, Center for Men\u2019s Health, Department of ART, Institute of Urology, Urologic Medical Center, Shanghai Key Laboratory of Reproductive Medicine, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine , Shanghai 200080 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yifan","family":"Sun","sequence":"additional","affiliation":[{"name":"Department of Andrology, Center for Men\u2019s Health, Department of ART, Institute of Urology, Urologic Medical Center, Shanghai Key Laboratory of Reproductive Medicine, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine , Shanghai 200080 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haowei","family":"Bai","sequence":"additional","affiliation":[{"name":"Department of Andrology, Center for Men\u2019s Health, Department of ART, Institute of Urology, Urologic Medical Center, Shanghai Key Laboratory of Reproductive Medicine, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine , Shanghai 200080 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3781-8319","authenticated-orcid":false,"given":"Erlei","family":"Zhi","sequence":"additional","affiliation":[{"name":"Department of Andrology, Center for Men\u2019s Health, Department of ART, Institute of Urology, Urologic Medical Center, Shanghai Key Laboratory of Reproductive Medicine, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine , Shanghai 200080 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sha","family":"Han","sequence":"additional","affiliation":[{"name":"Department of Andrology, Center for Men\u2019s Health, Department of ART, Institute of Urology, Urologic Medical Center, Shanghai Key Laboratory of Reproductive Medicine, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine , Shanghai 200080 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huixing","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Andrology, Center for Men\u2019s Health, Department of ART, Institute of Urology, Urologic Medical Center, Shanghai Key Laboratory of Reproductive Medicine, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine , Shanghai 200080 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Zhang","sequence":"additional","affiliation":[{"name":"Reproductive Medicine Center, The Sixth Affiliated Hospital, Sun Yat-sen University , 26 Yuancun-er-heng Road, Guangzhou 510655 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dewei","family":"Qian","sequence":"additional","affiliation":[{"name":"Department of Urology, The Affiliated Taizhou Peoples Hospital of Nanjing Medical University, Taizhou School of Clinical Medicine, Nanjing Medical University , Taizhou 225300 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinjie","family":"Bu","sequence":"additional","affiliation":[{"name":"Department of Urology, The Affiliated Taizhou Peoples Hospital of Nanjing Medical University, Taizhou School of Clinical Medicine, Nanjing Medical University , Taizhou 225300 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuhua","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Andrology, Center for Men\u2019s Health, Department of ART, Institute of Urology, Urologic Medical Center, Shanghai Key Laboratory of Reproductive Medicine, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine , Shanghai 200080 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5709-1175","authenticated-orcid":false,"given":"Ruhui","family":"Tian","sequence":"additional","affiliation":[{"name":"Department of Andrology, Center for Men\u2019s Health, Department of ART, Institute of Urology, Urologic Medical Center, Shanghai Key Laboratory of Reproductive Medicine, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine , Shanghai 200080 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying","family":"Guo","sequence":"additional","affiliation":[{"name":"The International Peace Maternity and Child Health Hospital, Shanghai Key Laboratory of Embryo Original Disease, School of Medicine, Shanghai Jiao Tong University , Shanghai 200030 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinxing","family":"Lv","sequence":"additional","affiliation":[{"name":"Department of Reproduction, The Fourth Affiliated Hospital of Soochow University (Suzhou Dushu Lake Hospital) , Suzhou 215000 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1070-3466","authenticated-orcid":false,"given":"Liangyu","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Urology, The Fifth Affiliated Hospital of Sun Yat-sen University , Zhuhai 519000 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Urologic Medical Center, Shanghai Key Laboratory of Reproductive Medicine, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine , Shanghai 200080 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhi","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Developmental and Regenerative Biology,\u00a0School of Life Science and Technology, ShanghaiTech University , Shanghai 200120 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zheng","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Andrology, Center for Men\u2019s Health, Department of ART, Institute of Urology, Urologic Medical Center, Shanghai Key Laboratory of Reproductive Medicine, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine , Shanghai 200080 ,","place":["China"]},{"name":"State Key Laboratory of Reproductive Medicine and Offspring Health, Nanjing Medical University , Nanjing 211166 ,","place":["China"]},{"name":"Department of Urology, The Affiliated Taizhou Peoples Hospital of Nanjing Medical University, Taizhou School of Clinical Medicine, Nanjing Medical University , Taizhou 225300 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chencheng","family":"Yao","sequence":"additional","affiliation":[{"name":"Department of Andrology, Center for Men\u2019s Health, Department of ART, Institute of Urology, Urologic Medical Center, Shanghai Key Laboratory of Reproductive Medicine, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine , Shanghai 200080 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2026,6,8]]},"reference":[{"key":"2026062901114581100_B1","doi-asserted-by":"publisher","first-page":"319","DOI":"10.1016\/S0140-6736(20)32667-2","article-title":"Male 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recombination","volume":"52","author":"Joo","year":"2024","journal-title":"Nucleic Acids Res"},{"key":"2026062901114581100_B8","doi-asserted-by":"publisher","first-page":"181","DOI":"10.1007\/s00412-019-00714-8","article-title":"Crossing and zipping: molecular duties of the ZMM proteins in meiosis","volume":"128","author":"Pyatnitskaya","year":"2019","journal-title":"Chromosoma"},{"key":"2026062901114581100_B9","doi-asserted-by":"publisher","first-page":"47","DOI":"10.1016\/j.tig.2024.09.009","article-title":"Crossover recombination between homologous chromosomes in meiosis: recent progress and remaining mysteries","volume":"41","author":"Payero","year":"2025","journal-title":"Trends Genet"},{"key":"2026062901114581100_B10","doi-asserted-by":"publisher","first-page":"e2310542120","DOI":"10.1073\/pnas.2310542120","article-title":"HEI10 is subject to phase separation and mediates RPA1a degradation during meiotic interference-sensitive crossover 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