Academic Journal
Heavy metal ions exchange driven protein phosphorylation cascade functions in genomic instability in spermatocytes and male infertility
| العنوان: | Heavy metal ions exchange driven protein phosphorylation cascade functions in genomic instability in spermatocytes and male infertility |
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| المؤلفون: | Li, Ren-Yan, Yang, Dan, He, Yan-Ji, Zhou, Yong, Li, Cheng-Cheng, Li, Lian-Bing, Liao, Ming-Xing, Deng, Zhong-Liang, Zhao, Le-Tian, Zhang, Tian-Feng, Luo, Yong, Wang, Ying-Xiong, Gao, Yan-Fei |
| المساهمون: | National Natural Science Foundation of China, Chongqing Municipal Science and Technology Commission Fundamental Research, China Postdoctoral Science Foundation |
| المصدر: | Nucleic Acids Research ; volume 51, issue 7, page 3150-3165 ; ISSN 0305-1048 1362-4962 |
| بيانات النشر: | Oxford University Press (OUP) |
| سنة النشر: | 2023 |
| الوصف: | DNA double-strand breaks (DSBs) are functionally linked to genomic instability in spermatocytes and to male infertility. 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. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| DOI: | 10.1093/nar/gkad128 |
| الاتاحة: | https://doi.org/10.1093/nar/gkad128 https://academic.oup.com/nar/article-pdf/51/7/3150/49875597/gkad128.pdf |
| Rights: | https://creativecommons.org/licenses/by-nc/4.0/ |
| رقم الانضمام: | edsbas.E556B746 |
| قاعدة البيانات: | BASE |
| DOI: | 10.1093/nar/gkad128 |
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