Control of Genome Stability by EndoMS/NucS-Mediated Non-Canonical Mismatch Repair
The DNA repair endonuclease EndoMS/NucS is highly conserved in Archaea and Actinobacteria. This enzyme is able to recognize and cleave dsDNA carrying a mismatched base pair, and its activity is enhanced by the interaction with the sliding clamp of the replisome. Today, EndoMS/NucS has been establish...
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MDPI AG
2021-05-01
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| author | Esmeralda Cebrián-Sastre Isabel Martín-Blecua Sonia Gullón Jesús Blázquez Alfredo Castañeda-García |
| author_facet | Esmeralda Cebrián-Sastre Isabel Martín-Blecua Sonia Gullón Jesús Blázquez Alfredo Castañeda-García |
| author_sort | Esmeralda Cebrián-Sastre |
| collection | DOAJ |
| description | The DNA repair endonuclease EndoMS/NucS is highly conserved in Archaea and Actinobacteria. This enzyme is able to recognize and cleave dsDNA carrying a mismatched base pair, and its activity is enhanced by the interaction with the sliding clamp of the replisome. Today, EndoMS/NucS has been established as the key protein of a non-canonical mismatch repair (MMR) pathway, acting specifically in the repair of transitions and being essential for maintaining genome stability. Despite having some particularities, such as its lower activity on transversions and the inability to correct indels, EndoMS/NucS meets the main hallmarks of a MMR. Its absence leads to a hypermutator phenotype, a transition-biased mutational spectrum and an increase in homeologous recombination. Interestingly, polymorphic EndoMS/NucS variants with a possible effect in mutation rate have been detected in clinical isolates of the relevant actinobacterial pathogen <i>Mycobacterium tuberculosis</i>. Considering that MMR defects are often associated with the emergence of resistant bacteria, the existence of EndoMS/NucS-defective mutators could have an important role in the acquisition of antibiotic resistance in <i>M. tuberculosis</i>. Therefore, a further understanding of the EndoMS/NucS-mediated non-canonical MMR pathway may reveal new strategies to predict and fight drug resistance. This review is focused on the recent progress in NucS, with special emphasis on its effect on genome stability and evolvability in Actinobacteria. |
| first_indexed | 2024-03-10T11:04:24Z |
| format | Article |
| id | doaj.art-65e50d7a5375484db0828e7e35827bc0 |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-10T11:04:24Z |
| publishDate | 2021-05-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj.art-65e50d7a5375484db0828e7e35827bc02023-11-21T21:17:51ZengMDPI AGCells2073-44092021-05-01106131410.3390/cells10061314Control of Genome Stability by EndoMS/NucS-Mediated Non-Canonical Mismatch RepairEsmeralda Cebrián-Sastre0Isabel Martín-Blecua1Sonia Gullón2Jesús Blázquez3Alfredo Castañeda-García4Centro Nacional de Biotecnología, Department of Microbial Biotechnology, Consejo Superior de Investigaciones Científicas (CSIC), 28049 Madrid, SpainCentro Nacional de Biotecnología, Department of Microbial Biotechnology, Consejo Superior de Investigaciones Científicas (CSIC), 28049 Madrid, SpainCentro Nacional de Biotecnología, Department of Microbial Biotechnology, Consejo Superior de Investigaciones Científicas (CSIC), 28049 Madrid, SpainCentro Nacional de Biotecnología, Department of Microbial Biotechnology, Consejo Superior de Investigaciones Científicas (CSIC), 28049 Madrid, SpainCentro Nacional de Biotecnología, Department of Microbial Biotechnology, Consejo Superior de Investigaciones Científicas (CSIC), 28049 Madrid, SpainThe DNA repair endonuclease EndoMS/NucS is highly conserved in Archaea and Actinobacteria. This enzyme is able to recognize and cleave dsDNA carrying a mismatched base pair, and its activity is enhanced by the interaction with the sliding clamp of the replisome. Today, EndoMS/NucS has been established as the key protein of a non-canonical mismatch repair (MMR) pathway, acting specifically in the repair of transitions and being essential for maintaining genome stability. Despite having some particularities, such as its lower activity on transversions and the inability to correct indels, EndoMS/NucS meets the main hallmarks of a MMR. Its absence leads to a hypermutator phenotype, a transition-biased mutational spectrum and an increase in homeologous recombination. Interestingly, polymorphic EndoMS/NucS variants with a possible effect in mutation rate have been detected in clinical isolates of the relevant actinobacterial pathogen <i>Mycobacterium tuberculosis</i>. Considering that MMR defects are often associated with the emergence of resistant bacteria, the existence of EndoMS/NucS-defective mutators could have an important role in the acquisition of antibiotic resistance in <i>M. tuberculosis</i>. Therefore, a further understanding of the EndoMS/NucS-mediated non-canonical MMR pathway may reveal new strategies to predict and fight drug resistance. This review is focused on the recent progress in NucS, with special emphasis on its effect on genome stability and evolvability in Actinobacteria.https://www.mdpi.com/2073-4409/10/6/1314EndoMS/NucSnon-canonical mismatch repairgenome stabilityhypermutationantibiotic resistanceActinobacteria |
| spellingShingle | Esmeralda Cebrián-Sastre Isabel Martín-Blecua Sonia Gullón Jesús Blázquez Alfredo Castañeda-García Control of Genome Stability by EndoMS/NucS-Mediated Non-Canonical Mismatch Repair Cells EndoMS/NucS non-canonical mismatch repair genome stability hypermutation antibiotic resistance Actinobacteria |
| title | Control of Genome Stability by EndoMS/NucS-Mediated Non-Canonical Mismatch Repair |
| title_full | Control of Genome Stability by EndoMS/NucS-Mediated Non-Canonical Mismatch Repair |
| title_fullStr | Control of Genome Stability by EndoMS/NucS-Mediated Non-Canonical Mismatch Repair |
| title_full_unstemmed | Control of Genome Stability by EndoMS/NucS-Mediated Non-Canonical Mismatch Repair |
| title_short | Control of Genome Stability by EndoMS/NucS-Mediated Non-Canonical Mismatch Repair |
| title_sort | control of genome stability by endoms nucs mediated non canonical mismatch repair |
| topic | EndoMS/NucS non-canonical mismatch repair genome stability hypermutation antibiotic resistance Actinobacteria |
| url | https://www.mdpi.com/2073-4409/10/6/1314 |
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