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...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2023-12-01
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| Series: | International Journal of Molecular Sciences |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1422-0067/24/24/17619 |
| Summary: | 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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| ISSN: | 1661-6596 1422-0067 |