The dual nature of mismatch repair as antimutator and mutator: for better or for worse
DNA is constantly under attack by a number of both exogenous and endogenous agents that challenge its integrity. Among the mechanisms that have evolved to counteract this deleterious action, mismatch repair (MMR) has specialized in removing DNA biosynthetic errors that occur when replicating the gen...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2014-08-01
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| Series: | Frontiers in Genetics |
| Subjects: | |
| Online Access: | http://journal.frontiersin.org/Journal/10.3389/fgene.2014.00287/full |
| _version_ | 1819274395585085440 |
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| author | Sara Thornby Bak Despoina eSakellariou Javier ePena-Diaz |
| author_facet | Sara Thornby Bak Despoina eSakellariou Javier ePena-Diaz |
| author_sort | Sara Thornby Bak |
| collection | DOAJ |
| description | DNA is constantly under attack by a number of both exogenous and endogenous agents that challenge its integrity. Among the mechanisms that have evolved to counteract this deleterious action, mismatch repair (MMR) has specialized in removing DNA biosynthetic errors that occur when replicating the genome. Malfunction or inactivation of this system results in an increase in spontaneous mutability and a strong predisposition to tumor development. Besides this key corrective role, MMR proteins are involved in other pathways of DNA metabolism such as mitotic and meiotic recombination and processing of oxidative damage. Surprisingly, MMR is also required for certain mutagenic processes. The mutagenic MMR has beneficial consequences contributing to the generation of a vast repertoire of antibodies through class switch recombination and somatic hypermutation processes. However, this non-canonical mutagenic MMR also has detrimental effects; it promotes repeat expansions associated with neuromuscular and neurodegenerative diseases and may contribute to cancer/disease-related aberrant mutations and translocations. The reaction responsible for replication error correction has been the most thoroughly studied and it is the subject to numerous reviews. This review describes briefly the biochemistry of MMR and focuses primarily on the non-canonical MMR activities described in mammals as well as emerging research implicating interplay of MMR and chromatin. |
| first_indexed | 2024-12-23T23:07:45Z |
| format | Article |
| id | doaj.art-0bbf207c657f47219c6296447b9458e8 |
| institution | Directory Open Access Journal |
| issn | 1664-8021 |
| language | English |
| last_indexed | 2024-12-23T23:07:45Z |
| publishDate | 2014-08-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Genetics |
| spelling | doaj.art-0bbf207c657f47219c6296447b9458e82022-12-21T17:26:45ZengFrontiers Media S.A.Frontiers in Genetics1664-80212014-08-01510.3389/fgene.2014.00287104785The dual nature of mismatch repair as antimutator and mutator: for better or for worseSara Thornby Bak0Despoina eSakellariou1Javier ePena-Diaz2University of CopenhagenUniversity of CopenhagenUniversity of CopenhagenDNA is constantly under attack by a number of both exogenous and endogenous agents that challenge its integrity. Among the mechanisms that have evolved to counteract this deleterious action, mismatch repair (MMR) has specialized in removing DNA biosynthetic errors that occur when replicating the genome. Malfunction or inactivation of this system results in an increase in spontaneous mutability and a strong predisposition to tumor development. Besides this key corrective role, MMR proteins are involved in other pathways of DNA metabolism such as mitotic and meiotic recombination and processing of oxidative damage. Surprisingly, MMR is also required for certain mutagenic processes. The mutagenic MMR has beneficial consequences contributing to the generation of a vast repertoire of antibodies through class switch recombination and somatic hypermutation processes. However, this non-canonical mutagenic MMR also has detrimental effects; it promotes repeat expansions associated with neuromuscular and neurodegenerative diseases and may contribute to cancer/disease-related aberrant mutations and translocations. The reaction responsible for replication error correction has been the most thoroughly studied and it is the subject to numerous reviews. This review describes briefly the biochemistry of MMR and focuses primarily on the non-canonical MMR activities described in mammals as well as emerging research implicating interplay of MMR and chromatin.http://journal.frontiersin.org/Journal/10.3389/fgene.2014.00287/fullNeurodegenerative DiseasesTrinucleotide RepeatsClass switch recombinationsomatic hypermutationnon-canonical mismatch repairantibody diversification |
| spellingShingle | Sara Thornby Bak Despoina eSakellariou Javier ePena-Diaz The dual nature of mismatch repair as antimutator and mutator: for better or for worse Frontiers in Genetics Neurodegenerative Diseases Trinucleotide Repeats Class switch recombination somatic hypermutation non-canonical mismatch repair antibody diversification |
| title | The dual nature of mismatch repair as antimutator and mutator: for better or for worse |
| title_full | The dual nature of mismatch repair as antimutator and mutator: for better or for worse |
| title_fullStr | The dual nature of mismatch repair as antimutator and mutator: for better or for worse |
| title_full_unstemmed | The dual nature of mismatch repair as antimutator and mutator: for better or for worse |
| title_short | The dual nature of mismatch repair as antimutator and mutator: for better or for worse |
| title_sort | dual nature of mismatch repair as antimutator and mutator for better or for worse |
| topic | Neurodegenerative Diseases Trinucleotide Repeats Class switch recombination somatic hypermutation non-canonical mismatch repair antibody diversification |
| url | http://journal.frontiersin.org/Journal/10.3389/fgene.2014.00287/full |
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