Mismatch Repair Protein Msh6<sup>Tt</sup> Is Necessary for Nuclear Division and Gametogenesis in <i>Tetrahymena thermophila</i>
DNA mismatch repair (MMR) improves replication accuracy by up to three orders of magnitude. The MutS protein in <i>E. coli</i> or its eukaryotic homolog, the MutSα (Msh2-Msh6) complex, recognizes base mismatches and initiates the mismatch repair mechanism. Msh6 is an essential protein fo...
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MDPI AG
2023-12-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/24/24/17619 |
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| author | Lin Wang Sitong Yang Yuhuan Xue Tao Bo Jing Xu Wei Wang |
| author_facet | Lin Wang Sitong Yang Yuhuan Xue Tao Bo Jing Xu Wei Wang |
| author_sort | Lin Wang |
| collection | DOAJ |
| description | DNA mismatch repair (MMR) improves replication accuracy by up to three orders of magnitude. The MutS protein in <i>E. coli</i> or its eukaryotic homolog, the MutSα (Msh2-Msh6) complex, recognizes base mismatches and initiates the mismatch repair mechanism. Msh6 is an essential protein for assembling the heterodimeric complex. However, the function of the Msh6 subunit remains elusive. <i>Tetrahymena</i> undergoes multiple DNA replication and nuclear division processes, including mitosis, amitosis, and meiosis. Here, we found that Msh6<sup>Tt</sup> localized in the macronucleus (MAC) and the micronucleus (MIC) during the vegetative growth stage and starvation. During the conjugation stage, Msh6<sup>Tt</sup> only localized in MICs and newly developing MACs. <i>MSH6<sup>Tt</sup></i> knockout led to aberrant nuclear division during vegetative growth. The <i>MSH6<sup>Tt</sup>KO</i> mutants were resistant to treatment with the DNA alkylating agent methyl methanesulfonate (MMS) compared to wild type cells. <i>MSH6<sup>Tt</sup></i> knockout affected micronuclear meiosis and gametogenesis during the conjugation stage. Furthermore, Msh6<sup>Tt</sup> interacted with Msh2<sup>Tt</sup> and MMR-independent factors. Downregulation of <i>MSH2<sup>Tt</sup></i> expression affected the stability of Msh6<sup>Tt</sup>. In addition, <i>MSH6<sup>Tt</sup></i> knockout led to the upregulated expression of several <i>MSH6<sup>Tt</sup></i> homologs at different developmental stages. Msh6<sup>Tt</sup> is involved in macronuclear amitosis, micronuclear mitosis, micronuclear meiosis, and gametogenesis in <i>Tetrahymena</i>. |
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| language | English |
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| spelling | doaj.art-bc42d8f7ae2441a08e11ba80bd9c07382023-12-22T14:15:23ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-12-0124241761910.3390/ijms242417619Mismatch Repair Protein Msh6<sup>Tt</sup> Is Necessary for Nuclear Division and Gametogenesis in <i>Tetrahymena thermophila</i>Lin Wang0Sitong Yang1Yuhuan Xue2Tao Bo3Jing Xu4Wei Wang5Key Laboratory of Chemical Biology and Molecular Engineering of Ministry of Education, Institute of Biotechnology, Shanxi University, Taiyuan 030006, ChinaKey Laboratory of Chemical Biology and Molecular Engineering of Ministry of Education, Institute of Biotechnology, Shanxi University, Taiyuan 030006, ChinaKey Laboratory of Chemical Biology and Molecular Engineering of Ministry of Education, Institute of Biotechnology, Shanxi University, Taiyuan 030006, ChinaKey Laboratory of Chemical Biology and Molecular Engineering of Ministry of Education, Institute of Biotechnology, Shanxi University, Taiyuan 030006, ChinaKey Laboratory of Chemical Biology and Molecular Engineering of Ministry of Education, Institute of Biotechnology, Shanxi University, Taiyuan 030006, ChinaKey Laboratory of Chemical Biology and Molecular Engineering of Ministry of Education, Institute of Biotechnology, Shanxi University, Taiyuan 030006, ChinaDNA mismatch repair (MMR) improves replication accuracy by up to three orders of magnitude. The MutS protein in <i>E. coli</i> or its eukaryotic homolog, the MutSα (Msh2-Msh6) complex, recognizes base mismatches and initiates the mismatch repair mechanism. Msh6 is an essential protein for assembling the heterodimeric complex. However, the function of the Msh6 subunit remains elusive. <i>Tetrahymena</i> undergoes multiple DNA replication and nuclear division processes, including mitosis, amitosis, and meiosis. Here, we found that Msh6<sup>Tt</sup> localized in the macronucleus (MAC) and the micronucleus (MIC) during the vegetative growth stage and starvation. During the conjugation stage, Msh6<sup>Tt</sup> only localized in MICs and newly developing MACs. <i>MSH6<sup>Tt</sup></i> knockout led to aberrant nuclear division during vegetative growth. The <i>MSH6<sup>Tt</sup>KO</i> mutants were resistant to treatment with the DNA alkylating agent methyl methanesulfonate (MMS) compared to wild type cells. <i>MSH6<sup>Tt</sup></i> knockout affected micronuclear meiosis and gametogenesis during the conjugation stage. Furthermore, Msh6<sup>Tt</sup> interacted with Msh2<sup>Tt</sup> and MMR-independent factors. Downregulation of <i>MSH2<sup>Tt</sup></i> expression affected the stability of Msh6<sup>Tt</sup>. In addition, <i>MSH6<sup>Tt</sup></i> knockout led to the upregulated expression of several <i>MSH6<sup>Tt</sup></i> homologs at different developmental stages. Msh6<sup>Tt</sup> is involved in macronuclear amitosis, micronuclear mitosis, micronuclear meiosis, and gametogenesis in <i>Tetrahymena</i>.https://www.mdpi.com/1422-0067/24/24/17619<i>Tetrahymena thermophila</i>mismatch repair protein Msh6<sup>Tt</sup>nuclear divisiongametogenesis |
| spellingShingle | Lin Wang Sitong Yang Yuhuan Xue Tao Bo Jing Xu Wei Wang Mismatch Repair Protein Msh6<sup>Tt</sup> Is Necessary for Nuclear Division and Gametogenesis in <i>Tetrahymena thermophila</i> International Journal of Molecular Sciences <i>Tetrahymena thermophila</i> mismatch repair protein Msh6<sup>Tt</sup> nuclear division gametogenesis |
| title | Mismatch Repair Protein Msh6<sup>Tt</sup> Is Necessary for Nuclear Division and Gametogenesis in <i>Tetrahymena thermophila</i> |
| title_full | Mismatch Repair Protein Msh6<sup>Tt</sup> Is Necessary for Nuclear Division and Gametogenesis in <i>Tetrahymena thermophila</i> |
| title_fullStr | Mismatch Repair Protein Msh6<sup>Tt</sup> Is Necessary for Nuclear Division and Gametogenesis in <i>Tetrahymena thermophila</i> |
| title_full_unstemmed | Mismatch Repair Protein Msh6<sup>Tt</sup> Is Necessary for Nuclear Division and Gametogenesis in <i>Tetrahymena thermophila</i> |
| title_short | Mismatch Repair Protein Msh6<sup>Tt</sup> Is Necessary for Nuclear Division and Gametogenesis in <i>Tetrahymena thermophila</i> |
| title_sort | mismatch repair protein msh6 sup tt sup is necessary for nuclear division and gametogenesis in i tetrahymena thermophila i |
| topic | <i>Tetrahymena thermophila</i> mismatch repair protein Msh6<sup>Tt</sup> nuclear division gametogenesis |
| url | https://www.mdpi.com/1422-0067/24/24/17619 |
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