Definition and research guide
This page combines a MeSH definition, publication statistics and selected research abstracts. It is a starting point for reading the literature, not a medical textbook or a systematic evidence review.
Content available: 4 complete abstracts (638 words), 10 references. Full article text is not stored or reproduced here; follow the PMID, DOI or PMC links to read the original sources and their access terms.
Definition
A DNA repair pathway involved in correction of errors introduced during DNA replication when an incorrect base, which cannot form hydrogen bonds with the corresponding base in the parent strand, is incorporated into the daughter strand. Excinucleases recognize the base pair mismatch and cause a segment of polynucleotide chain to be excised from the daughter strand, thereby removing the mismatched base. (from Oxford Dictionary of Biochemistry and Molecular Biology, 2001)
Definition: NLM Medical Subject Headings (MeSH) scope note (Public domain (U.S. National Library of Medicine); attribution requested). View the MeSH record.
Also known as: Mismatch Repair, DNA; Repair, DNA Mismatch; Mismatch Repair; Repair, Mismatch.
Where it fits in the MeSH classification
- Broader topics
- DNA Repair
Related concepts
- Base Pair Mismatch
Research landscape
PubMed indexes 5,139 records tagged with the MeSH heading “DNA Mismatch Repair” (counts retrieved 2026-10-29). 2,339 of them (45.5%) were published from 2020 onward, and the busiest period so far is 2020 onward with 2,339 records.
Reviews account for 818 records (15.9%) and meta-analyses for 65. Randomized controlled trials number 56 (1.1%) as a share of all records on the topic. Randomized trials make up only a small share of this literature, so much of what is known comes from laboratory, observational or descriptive work.
Show the data
| Period | Records |
|---|---|
| through 1999 | 0 |
| 2000-2009 | 637 |
| 2010-2019 | 2,239 |
| 2020 onward | 2,339 |
Publication-type chart data
| Type | Records | Share |
|---|---|---|
| Reviews | 818 | 15.9% |
| Meta-analyses | 65 | 1.3% |
| Randomized controlled trials | 56 | 1.1% |
Method: PubMed query "DNA Mismatch Repair"[MeSH Terms] with publication-type and date filters, retrieved 2026-10-29.
Reading the evidence in molecular biology
Molecular biology establishes mechanisms through controlled experiments, often in simplified systems such as purified proteins, cultured cells or model organisms. Such work can show what is possible in a defined system, but whether a pathway matters in a whole organism or in human disease needs further evidence. Check the experimental system, whether findings were reproduced by independent groups, and whether the authors tested the mechanism directly or inferred it from correlation.
Evidence from open-access studies
These open-access studies come from PubMed’s best-match results for this heading (papers whose main topic it is), ranked here by citation count, with one recent addition. Each abstract is reproduced in full under its recorded open licence so that you can read the authors’ own words. They illustrate the literature; they are not a systematic summary of it. Citation counts measure attention, not reliability or clinical benefit.
| Study / authors | Year | Source label / design | Europe PMC citations | Licence / source |
|---|---|---|---|---|
| Structural basis for mismatch surveillance by CRISPR-Cas9 | 2022 | Research article Design not recorded in structured metadata | 229 | cc by PMID 35236982 · DOI · PMC8907077 |
| Prime editing efficiency and fidelity are enhanced in the absence of mismatch repair | 2022 | Research article Design not recorded in structured metadata | 163 | cc by PMID 35140211 · DOI · PMC8828784 |
| Structural basis of mismatch recognition by a SARS-CoV-2 proofreading enzyme | 2021 | Research article Design not recorded in structured metadata | 135 | cc by PMID 34315827 · DOI · PMC9836006 |
| Mismatch repair deficiency drives malignant progression and alters the tumor immune microenvironment in glioblastoma models | 2026 | Research article Design not recorded in structured metadata | 5 | cc by PMID 41433099 · DOI · PMC12987617 |
Structural basis for mismatch surveillance by CRISPR-Cas9 [1]
Abstract reading summary — source excerpts
- Opening excerpt
- CRISPR-Cas9 as a programmable genome editing tool is hindered by off-target DNA cleavage1-4, and the underlying mechanisms by which Cas9 recognizes mismatches are poorly understood5-7.
- Closing excerpt
- By targeting regions that are exclusively involved in mismatch tolerance, we provide a proof of concept for the design of next-generation high-fidelity Cas9 variants.
- Interpretation limits
- Verbatim excerpts from the authors’ abstract; the closing excerpt may describe a finding, limitation or recommendation. Design, population, effect size and uncertainty have not been independently extracted or appraised. Read the complete abstract and linked paper before interpreting the findings.
Read complete abstract (158 words)
CRISPR-Cas9 as a programmable genome editing tool is hindered by off-target DNA cleavage1-4, and the underlying mechanisms by which Cas9 recognizes mismatches are poorly understood5-7. Although Cas9 variants with greater discrimination against mismatches have been designed8-10, these suffer from substantially reduced rates of on-target DNA cleavage5,11. Here we used kinetics-guided cryo-electron microscopy to determine the structure of Cas9 at different stages of mismatch cleavage. We observed a distinct, linear conformation of the guide RNA-DNA duplex formed in the presence of mismatches, which prevents Cas9 activation. Although the canonical kinked guide RNA-DNA duplex conformation facilitates DNA cleavage, we observe that substrates that contain mismatches distal to the protospacer adjacent motif are stabilized by reorganization of a loop in the RuvC domain. Mutagenesis of mismatch-stabilizing residues reduces off-target DNA cleavage but maintains rapid on-target DNA cleavage. By targeting regions that are exclusively involved in mismatch tolerance, we provide a proof of concept for the design of next-generation high-fidelity Cas9 variants.
Abstract reproduced from the open-access article under the recorded cc by licence; © the authors. PMID 35236982 · DOI · PMC8907077
Prime editing efficiency and fidelity are enhanced in the absence of mismatch repair [2]
Abstract reading summary — source excerpts
- Opening excerpt
- Prime editing (PE) is a powerful genome engineering approach that enables the introduction of base substitutions, insertions and deletions into any given genomic locus.
- Closing excerpt
- Our results shed new light on the mechanism of PE and suggest how its efficiency might be optimised.
- Interpretation limits
- Verbatim excerpts from the authors’ abstract; the closing excerpt may describe a finding, limitation or recommendation. Design, population, effect size and uncertainty have not been independently extracted or appraised. Read the complete abstract and linked paper before interpreting the findings.
Read complete abstract (151 words)
Prime editing (PE) is a powerful genome engineering approach that enables the introduction of base substitutions, insertions and deletions into any given genomic locus. However, the efficiency of PE varies widely and depends not only on the genomic region targeted, but also on the genetic background of the edited cell. Here, to determine which cellular factors affect PE efficiency, we carry out a focused genetic screen targeting 32 DNA repair factors, spanning all reported repair pathways. We show that, depending on cell line and type of edit, ablation of mismatch repair (MMR) affords a 2-17 fold increase in PE efficiency, across several human cell lines, types of edits and genomic loci. The accumulation of the key MMR factors MLH1 and MSH2 at PE sites argues for direct involvement of MMR in PE control. Our results shed new light on the mechanism of PE and suggest how its efficiency might be optimised.
Abstract reproduced from the open-access article under the recorded cc by licence; © the authors. PMID 35140211 · DOI · PMC8828784
Structural basis of mismatch recognition by a SARS-CoV-2 proofreading enzyme [3]
Abstract reading summary — source excerpts
- Opening excerpt
- Coronavirus 3′-to-5′ exoribonuclease (ExoN), residing in the nonstructural protein (nsp) 10–nsp14 complex, boosts replication fidelity by proofreading RNA synthesis and is critical for the virus life cycle.
- Closing excerpt
- Our findings provide guidance for rational design of improved anticoronavirus therapies.
- Interpretation limits
- Verbatim excerpts from the authors’ abstract; the closing excerpt may describe a finding, limitation or recommendation. Design, population, effect size and uncertainty have not been independently extracted or appraised. Read the complete abstract and linked paper before interpreting the findings.
Read complete abstract (119 words)
Coronavirus 3′-to-5′ exoribonuclease (ExoN), residing in the nonstructural protein (nsp) 10–nsp14 complex, boosts replication fidelity by proofreading RNA synthesis and is critical for the virus life cycle. ExoN also recognizes and excises nucleotide analog inhibitors incorporated into the nascent RNA, undermining the effectiveness of nucleotide analog–based antivirals. Here we present cryo–electron microscopy structures of both wild-type and mutant severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) nsp10-nsp14 in complex with an RNA substrate bearing a 3′-end mismatch at resolutions ranging from 2.5 to 3.9 angstroms. The structures reveal the molecular determinants of ExoN substrate specificity and offer insight into the molecular mechanisms of mismatch correction during coronavirus RNA synthesis. Our findings provide guidance for rational design of improved anticoronavirus therapies.
Abstract reproduced from the open-access article under the recorded cc by licence; © the authors. PMID 34315827 · DOI · PMC9836006
Mismatch repair deficiency drives malignant progression and alters the tumor immune microenvironment in glioblastoma models [4]
Abstract reading summary — source excerpts
- Opening excerpt
- Mutations in DNA mismatch repair (MMR) pathway genes (MSH2, MSH6, MLH1, and PMS2) are linked to acquired resistance to temozolomide (TMZ) and high tumor mutation burden (TMB) in high-grade gliomas (HGGs), including glioblastomas (GBMs).
- Closing excerpt
- Our study shows that N3-(2-fluoroethyl) imidazotetrazine (KL-50), an imidazotetrazine-based DNA targeting agent that induces MMR-independent cross-link-mediated cytotoxicity, was effective against germline and somatic MMRr and MMRd GBMs, offering a potential therapy for TMZ-resistant HGG with MMR alterations.
- Interpretation limits
- Verbatim excerpts from the authors’ abstract; the closing excerpt may describe a finding, limitation or recommendation. Design, population, effect size and uncertainty have not been independently extracted or appraised. Read the complete abstract and linked paper before interpreting the findings.
Read complete abstract (210 words)
Mutations in DNA mismatch repair (MMR) pathway genes (MSH2, MSH6, MLH1, and PMS2) are linked to acquired resistance to temozolomide (TMZ) and high tumor mutation burden (TMB) in high-grade gliomas (HGGs), including glioblastomas (GBMs). However, the specific roles of individual MMR genes in the initiation, progression, TMB, microsatellite instability (MSI), and resistance to TMZ in gliomas remain unclear. Here, we developed de novo mouse models of germline and somatic MMR-deficient (MMRd) HGGs. Surprisingly, loss of Msh2 or Msh6 did not lead to high TMB, MSI, nor did it confer a response to anti-programmed cell death 1 (anti-PD-1) in GBM. Similarly, human GBM showed discordance between MMR gene mutations and the TMB and MSI. Germline MMRd promoted the progression from low-grade to HGG and reduced survival compared with MMR-proficient (MMRp) tumor-bearing mice. This effect was not tumor cell intrinsic but was associated with MMRd in the tumor immune microenvironment, driving immunosuppressive myeloid programs, reduced lymphoid infiltration, and CD8+ T cell exhaustion. Both MMR-reduced (MMRr) and MMRd GBM were resistant to TMZ, unlike MMRp tumors. Our study shows that N3-(2-fluoroethyl) imidazotetrazine (KL-50), an imidazotetrazine-based DNA targeting agent that induces MMR-independent cross-link-mediated cytotoxicity, was effective against germline and somatic MMRr and MMRd GBMs, offering a potential therapy for TMZ-resistant HGG with MMR alterations.
Abstract reproduced from the open-access article under the recorded cc by licence; © the authors. PMID 41433099 · DOI · PMC12987617
Key reviews and meta-analyses
The most cited review-type papers among PubMed’s best-match results for this heading, listed with bibliographic details only. Follow the links for the full text and access terms.
- Research article Mechanisms and functions of DNA mismatch repair [5]
- Research article Milestones of Lynch syndrome: 1895-2015 [6]
- Research article Mismatch repair deficiency/microsatellite instability-high as a predictor for anti-PD-1/PD-L1 immunotherapy efficacy [7]
- Research article DNA mismatch repair in cancer [8]
- Research article Eukaryotic Mismatch Repair in Relation to DNA Replication [9]
- Research article DNA mismatch repair: molecular mechanism, cancer, and ageing [10]
References
- Bravo JPK, Liu MS, Hibshman GN, Dangerfield TL, Jung K, McCool RS, et al.. Structural basis for mismatch surveillance by CRISPR-Cas9. . 2022. PMID 35236982 · DOI · PMC8907077
- Ferreira da Silva J, Oliveira GP, Arasa-Verge EA, Kagiou C, Moretton A, Timelthaler G, et al.. Prime editing efficiency and fidelity are enhanced in the absence of mismatch repair. . 2022. PMID 35140211 · DOI · PMC8828784
- Liu C, Shi W, Becker ST, Schatz DG, Liu B, Yang Y. Structural basis of mismatch recognition by a SARS-CoV-2 proofreading enzyme. . 2021. PMID 34315827 · DOI · PMC9836006
- Puigdelloses Vallcorba M, Soni N, Choi SW, Rawat K, Joshi T, Friedman S, et al.. Mismatch repair deficiency drives malignant progression and alters the tumor immune microenvironment in glioblastoma models. . 2026. PMID 41433099 · DOI · PMC12987617
- Li GM. Mechanisms and functions of DNA mismatch repair. Cell Res. 2008. PMID 18157157 · DOI
- Lynch HT, Snyder CL, Shaw TG, Heinen CD, Hitchins MP. Milestones of Lynch syndrome: 1895-2015. Nat Rev Cancer. 2015. PMID 25673086 · DOI
- Zhao P, Li L, Jiang X, Li Q. Mismatch repair deficiency/microsatellite instability-high as a predictor for anti-PD-1/PD-L1 immunotherapy efficacy. J Hematol Oncol. 2019. PMID 31151482 · DOI · PMC6544911
- Baretti M, Le DT. DNA mismatch repair in cancer. Pharmacol Ther. 2018. PMID 29669262 · DOI
- Kunkel TA, Erie DA. Eukaryotic Mismatch Repair in Relation to DNA Replication. Annu Rev Genet. 2015. PMID 26436461 · DOI · PMC5439269
- Hsieh P, Yamane K. DNA mismatch repair: molecular mechanism, cancer, and ageing. Mech Ageing Dev. 2008. PMID 18406444 · DOI · PMC2574955
About this article
- Sources
- NLM Medical Subject Headings (definition, synonyms); NCBI PubMed (counts, identifiers); Europe PMC (open-access abstracts and citation counts).
- Verification
- Every reference was resolved against PubMed on 2026-10-31; title, year and DOI matched.
- Review state
- automated source verified; no human expert review has been recorded yet.
- Version
- 1, last updated 2026-10-29.
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Evidence strength
EvidenceHelix's computed view of the study designs behind this topic: how common meta-analyses, randomized trials and reviews are, how recent the literature is, and a plain-language reading. It describes the design mix of the literature. It is not a quality appraisal of any study, and it is not medical advice.