H2B ubiquitination: Conserved molecular mechanism, diverse physiologic functions of the E3 ligase during meiosis
| Autor: | Chunwei Cao, Jianguo Zhao, Fang Wang, Liying Wang, Wei Li |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Male DNA Repair Ubiquitin-Protein Ligases Evolution Molecular Histones 03 medical and health sciences Mice Meiosis Ubiquitin Spermatocytes Humans Animals DNA Breaks Double-Stranded Spermatogenesis Conserved Sequence Infertility Male Adaptor Proteins Signal Transducing Genetics Mice Knockout Recombination Genetic 030102 biochemistry & molecular biology Phylogenetic tree biology urogenital system Extra View Gene regulation Chromatin and Epigenetics Ubiquitination Cell Biology Chromatin Assembly and Disassembly Yeast Chromatin Ubiquitin ligase 030104 developmental biology Germ Cells biology.protein Molecular mechanism Female Pachytene Stage Homologous recombination |
| Zdroj: | Nucleic Acids Research |
| Popis: | Meiotic recombination is essential for fertility in most sexually reproducing species, but the molecular mechanisms underlying this process remain poorly understood in mammals. Here, we show that RNF20-mediated H2B ubiquitination is required for meiotic recombination. A germ cell-specific knockout of the H2B ubiquitination E3 ligase RNF20 results in complete male infertility. The Stra8-Rnf20−/− spermatocytes arrest at the pachytene stage because of impaired programmed double-strand break (DSB) repair. Further investigations reveal that the depletion of RNF20 in the germ cells affects chromatin relaxation, thus preventing programmed DSB repair factors from being recruited to proper positions on the chromatin. The gametogenetic defects of the H2B ubiquitination deficient cells could be partially rescued by forced chromatin relaxation. Taken together, our results demonstrate that RNF20/Bre1p-mediated H2B ubiquitination regulates meiotic recombination by promoting chromatin relaxation, and suggest an old drug may provide a new way to treat some oligo- or azoospermia patients with chromatin relaxation disorders. |
| Databáze: | OpenAIRE |
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