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The heavy metal cadmium (Cd) is known to induce DNA damage in spermatocytes by unknown mechanisms. Here, we showed that Cd ions impaired the canonical non-homologous end-joining (NHEJ) repair pathway, but not the homologous recombination (HR) repair pathway, through stimulation of Ser2056 and Thr2609 phosphorylation of DNA-PKcs at DSB sites. Hyper-phosphorylation of DNA-PKcs led to its premature dissociation from DNA ends and the Ku complex, preventing recruitment of processing enzymes and further ligation of DNA ends. Specifically, this cascade was initiated by the loss of PP5 phosphatase activity, which results from the dissociation of PP5 from its activating ions (Mn), that is antagonized by Cd ions through a competitive mechanism. In accordance, in a mouse model Cd-induced genomic instability and consequential male reproductive dysfunction were effectively reversed by a high dosage of Mn ions. Together, our findings corroborate a protein phosphorylation-mediated genomic instability pathway in spermatocytes that is triggered by exchange of heavy metal ions.<\/jats:p>","DOI":"10.1093\/nar\/gkad128","type":"journal-article","created":{"date-parts":[[2023,3,4]],"date-time":"2023-03-04T10:18:08Z","timestamp":1677925088000},"page":"3150-3165","source":"Crossref","is-referenced-by-count":13,"title":["Heavy metal ions exchange driven protein phosphorylation cascade functions in genomic instability in spermatocytes and male infertility"],"prefix":"10.1093","volume":"51","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8843-5185","authenticated-orcid":false,"given":"Ren-Yan","family":"Li","sequence":"first","affiliation":[{"name":"NHC Key Laboratory of Birth Defects and Reproductive Health, Chongqing Population and Family Planning Science and Technology Research Institute , Chongqing \u00a0401120, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dan","family":"Yang","sequence":"additional","affiliation":[{"name":"The Second Affiliated Hospital, Chongqing Medical University , Chongqing \u00a0400016, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yan-Ji","family":"He","sequence":"additional","affiliation":[{"name":"The Second Affiliated Hospital, Chongqing Medical University , Chongqing \u00a0400016, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yong","family":"Zhou","sequence":"additional","affiliation":[{"name":"The Second Affiliated Hospital, Chongqing Medical University , Chongqing \u00a0400016, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cheng-Cheng","family":"Li","sequence":"additional","affiliation":[{"name":"The Second Affiliated Hospital, Chongqing Medical University , Chongqing \u00a0400016, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lian-Bing","family":"Li","sequence":"additional","affiliation":[{"name":"NHC Key Laboratory of Birth Defects and Reproductive Health, Chongqing Population and Family Planning Science and Technology Research Institute , Chongqing \u00a0401120, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ming-Xing","family":"Liao","sequence":"additional","affiliation":[{"name":"NHC Key Laboratory of Birth Defects and Reproductive Health, Chongqing Population and Family Planning Science and Technology Research Institute , Chongqing \u00a0401120, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhong-Liang","family":"Deng","sequence":"additional","affiliation":[{"name":"The Second Affiliated Hospital, Chongqing Medical University , Chongqing \u00a0400016, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Le-Tian","family":"Zhao","sequence":"additional","affiliation":[{"name":"NHC Key Laboratory of Birth Defects and Reproductive Health, Chongqing Population and Family Planning Science and Technology Research Institute , Chongqing \u00a0401120, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tian-Feng","family":"Zhang","sequence":"additional","affiliation":[{"name":"NHC Key Laboratory of Birth Defects and Reproductive Health, Chongqing Population and Family Planning Science and Technology Research Institute , Chongqing \u00a0401120, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yong","family":"Luo","sequence":"additional","affiliation":[{"name":"The first Affiliated Hospital, Chongqing Medical University , Chongqing \u00a0400016, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ying-Xiong","family":"Wang","sequence":"additional","affiliation":[{"name":"Joint International Research Laboratory of Reproduction & Development, Chongqing Medical University , Chongqing \u00a0400016, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yan-Fei","family":"Gao","sequence":"additional","affiliation":[{"name":"School of Basic Medical Sciences, Chongqing Medical University , Chongqing \u00a0400016, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2023,3,3]]},"reference":[{"key":"2023042403071525800_B1","doi-asserted-by":"crossref","first-page":"158","DOI":"10.1016\/j.dnarep.2018.08.019","article-title":"DNA double-strand breaks as drivers of neural genomic change, function, and disease","volume":"71","author":"Alt","year":"2018","journal-title":"DNA Repair (Amst.)"},{"key":"2023042403071525800_B2","doi-asserted-by":"crossref","first-page":"10502","DOI":"10.1074\/jbc.TM118.000371","article-title":"How cells ensure correct repair of DNA double-strand breaks","volume":"293","author":"Her","year":"2018","journal-title":"J. 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Biol. Chem."},{"key":"2023042403071525800_B39","doi-asserted-by":"crossref","first-page":"5741","DOI":"10.1021\/ja513117p","article-title":"Mechanism of action studies of lomaiviticin A and the monomeric lomaiviticin aglycon. Selective and potent activity toward DNA double-strand break repair-deficient cell lines","volume":"137","author":"Colis","year":"2015","journal-title":"J. Am. Chem. 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Cell. Biol."},{"key":"2023042403071525800_B52","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1083\/jcb.200608077","article-title":"Autophosphorylation of DNA-PKCS regulates its dynamics at DNA double-strand breaks","volume":"177","author":"Uematsu","year":"2007","journal-title":"J. Cell Biol."},{"key":"2023042403071525800_B53","doi-asserted-by":"crossref","first-page":"1414","DOI":"10.1074\/jbc.M109.065615","article-title":"Ku and DNA-dependent protein kinase dynamic conformations and assembly regulate DNA binding and the initial non-homologous end joining complex","volume":"285","author":"Hammel","year":"2010","journal-title":"J. Biol. 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