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: 3 complete abstracts (493 words), 9 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
Injuries to DNA that introduce deviations from its normal, intact structure and which may, if left unrepaired, result in a mutation or a block of dna replication. These deviations may be caused by physical or chemical agents and occur by natural or unnatural, introduced circumstances. They include the introduction of illegitimate bases during replication or by deamination or other modification of bases; the loss of a base from the DNA backbone leaving an abasic site; single-strand breaks; double strand breaks; and intrastrand (pyrimidine dimers) or interstrand crosslinking. Damage can often be repaired (dna repair). If the damage is extensive, it can induce apoptosis.
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: Injury, DNA; DNA Injuries; DNA Injury; DNA Lesion; DNA Lesions; Genotoxic Stress; Stress, Genotoxic.
Where it fits in the MeSH classification
- Broader topics
- Genetic Phenomena
- Narrower topics
- Base Pair Mismatch; DNA Adducts; DNA Breaks; DNA Degradation, Necrotic; DNA Fragmentation; Pyrimidine Dimers
- See also
- Mutation
Related concepts
- Mutation
- Dna Replication
- Pyrimidine Dimers
- DNA Repair
- Apoptosis
Research landscape
PubMed indexes 122,416 records tagged with the MeSH heading “DNA Damage” (counts retrieved 2026-10-29). 21,031 of them (17.2%) were published from 2020 onward, and the busiest period so far is 2010-2019 with 43,291 records.
Reviews account for 15,090 records (12.3%) and meta-analyses for 186. Randomized controlled trials number 428 (0.3%) 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 | 20,071 |
| 2000-2009 | 38,023 |
| 2010-2019 | 43,291 |
| 2020 onward | 21,031 |
Publication-type chart data
| Type | Records | Share |
|---|---|---|
| Reviews | 15,090 | 12.3% |
| Meta-analyses | 186 | 0.2% |
| Randomized controlled trials | 428 | 0.3% |
Method: PubMed query "DNA Damage"[MeSH Terms] with publication-type and date filters, retrieved 2026-10-29.
Reading the evidence in genetics and genomics
Genetic findings vary widely in strength. A variant linked to a condition in one study may not replicate in other ancestries, and most common variants have small effects that are meaningful only in aggregate. Studies of rare, high-impact variants can support strong causal claims about a gene, while association studies describe statistical links that need functional and independent replication. Check the sample size, the ancestry of participants, whether results were replicated, and whether a laboratory or clinical outcome was actually measured.
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 |
|---|---|---|---|---|
| DNA damage burden causes selective CUX2 neuron loss in neuroinflammation | 2026 | Research article Design not recorded in structured metadata | 5 | cc by PMID 41922773 · DOI · PMC13190333 |
| Recurrent DNA break clusters drive replication-stress-induced copy number variants and genome diversification | 2026 | Research article Design not recorded in structured metadata | 4 | cc by PMID 42009664 · DOI · PMC13096501 |
| Mitotic microhomology-mediated break-induced replication promotes chromoanasynthesis | 2026 | Research article Design not recorded in structured metadata | 4 | cc by PMID 41775729 · DOI · PMC13065848 |
DNA damage burden causes selective CUX2 neuron loss in neuroinflammation [1]
Abstract reading summary — source excerpts
- Opening excerpt
- Neurodegeneration shows regional and cell-type-specific patterns in ageing and disease1, but the underlying mechanisms for cell-type-specific neuronal losses remain poorly understood.
- Closing excerpt
- These findings indicate that DNA damage burden and inadequate repair in CUX2+ L2/3ENs contributes to selective vulnerability in neuroinflammatory injury.
- 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 (177 words)
Neurodegeneration shows regional and cell-type-specific patterns in ageing and disease1, but the underlying mechanisms for cell-type-specific neuronal losses remain poorly understood. Previous studies have shown that upper cortical layer thinning occurs in progressive human multiple sclerosis (MS) and that cortical layer 2 and layer 3 (L2/3) excitatory neurons (L2/3ENs) that express CUT-like homeobox 2 (CUX2) are selectively vulnerable to degeneration2. Here we report that L2/3ENs within MS cortical lesions have an elevated DNA damage burden. DNA damage and selective loss of L2/3ENs were recapitulated in diverse mouse models of demyelination and pan-cortical inflammation, confirming their intrinsic vulnerability. Functions of Cux2 and activating transcription factor 4 (Atf4) were essential for resilience of L2/3ENs during postnatal neuroinflammation, acting in neurons to enhance DNA double-strand break repair. Interferon-γ, a cytokine implicated in MS pathogenesis3,4, was sufficient to elevate levels of reactive oxygen species, leading to DNA damage-mediated neuronal death in vitro, and caused selective depletion of L2/3 neurons in mice. These findings indicate that DNA damage burden and inadequate repair in CUX2+ L2/3ENs contributes to selective vulnerability in neuroinflammatory injury.
Abstract reproduced from the open-access article under the recorded cc by licence; © the authors. PMID 41922773 · DOI · PMC13190333
Recurrent DNA break clusters drive replication-stress-induced copy number variants and genome diversification [2]
Abstract reading summary — source excerpts
- Opening excerpt
- Copy number variants (CNVs) are strongly implicated in neurological and psychiatric disorders and brain cancer, yet the process by which replication stress generates CNVs-and why some recur while others remain rare-remains poorly understood.
- Closing excerpt
- Together, these findings define RDCs as central drivers of replication-stress-induced genome diversification.
- 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 (167 words)
Copy number variants (CNVs) are strongly implicated in neurological and psychiatric disorders and brain cancer, yet the process by which replication stress generates CNVs-and why some recur while others remain rare-remains poorly understood. Here, we show that recurrent DNA-break clusters (RDCs) act as common initiating lesions that drive both recurrent and non-recurrent CNVs. In murine neural progenitor cells subjected to chemically induced replication stress, bulk whole-genome sequencing identifies recurrent CNVs enriched at late-replicating RDCs within actively transcribed genes. Single-cell genome sequencing further uncovers frequent, non-recurrent CNVs associated with RDCs that arise during the transition from early to late DNA replication. These CNVs represent stable, heritable structural variants with breakpoints consistently enriched at RDCs. CRISPR/Cas9-mediated transcriptional suppression abolishes both RDC formation and CNV generation, establishing RDC-associated breaks as a shared upstream source. Mechanistically, CNV formation depends on DNA repair context: CNVs are Pol θ-dependent in NHEJ-deficient cells but arise independently of Pol θ in NHEJ-proficient cells. Together, these findings define RDCs as central drivers of replication-stress-induced genome diversification.
Abstract reproduced from the open-access article under the recorded cc by licence; © the authors. PMID 42009664 · DOI · PMC13096501
Mitotic microhomology-mediated break-induced replication promotes chromoanasynthesis [3]
Abstract reading summary — source excerpts
- Opening excerpt
- Chromoanasynthesis is a form of complex chromosomal rearrangement (CCR) commonly detected in cancers and congenital disorders, but the mechanism underlying its generation remain elusive.
- Closing excerpt
- Our findings help explain the extreme mutagenic nature of chromoanasynthesis and establish mitotic MM-BIR as a key driver of CCRs, with important implications for the origin of cancers and congenital disorders.
- 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 (149 words)
Chromoanasynthesis is a form of complex chromosomal rearrangement (CCR) commonly detected in cancers and congenital disorders, but the mechanism underlying its generation remain elusive. Here we develop a single-molecule long-read DNA sequencing approach to characterise ultra-complex mutational events, consistent with chromoanasynthesis, occurring at shortened telomeres and sub-telomeric DNA double-strand breaks in human cells. Our data reveal that chromoanasynthesis is generated by microhomology-mediated break-induced replication (MM-BIR), occurring specifically in mitosis. Surprisingly, this mitotic pathway involves a collaboration between microhomology-mediated end-joining (MMEJ) and BIR, where MMEJ proteins initiate a Polδ-dependent BIR pathway that is regulated by PIF1, POLD3 and PCNA. This pathway is highly prone to template switching and can generate dramatic amplification of genomic loci in a single event. Our findings help explain the extreme mutagenic nature of chromoanasynthesis and establish mitotic MM-BIR as a key driver of CCRs, with important implications for the origin of cancers and congenital disorders.
Abstract reproduced from the open-access article under the recorded cc by licence; © the authors. PMID 41775729 · DOI · PMC13065848
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 A systematic review and meta-analysis to determine the effect of sperm DNA damage on in vitro fertilization and intracytoplasmic sperm injection outcome [4]
- Research article The effect of sperm DNA fragmentation on live birth rate after IVF or ICSI: a systematic review and meta-analysis [5]
- Research article Sperm DNA fragmentation and recurrent pregnancy loss: a systematic review and meta-analysis [6]
- Research article Relationship between varicocele and sperm DNA damage and the effect of varicocele repair: a meta-analysis [7]
- Research article Pathogenesis of DNA repair-deficient cancers: a statistical meta-analysis of putative Real Common Target genes [8]
- Research article Correlation of sperm DNA damage with IVF and ICSI outcomes: a systematic review and meta-analysis [9]
References
- Morcom L, Xia W, Xu Z, Awasthi Y, Geywitz C, Ellis MO, et al.. DNA damage burden causes selective CUX2 neuron loss in neuroinflammation. . 2026. PMID 41922773 · DOI · PMC13190333
- Corazzi L, Ing A, Benito E, Cosenza MR, Hasenfeld P, Weber T, et al.. Recurrent DNA break clusters drive replication-stress-induced copy number variants and genome diversification. . 2026. PMID 42009664 · DOI · PMC13096501
- Ngo GHP, Cleal K, Seifan S, Miklos V, Barwacz SA, Ruis BL, et al.. Mitotic microhomology-mediated break-induced replication promotes chromoanasynthesis. . 2026. PMID 41775729 · DOI · PMC13065848
- Simon L, Zini A, Dyachenko A, Ciampi A, Carrell DT. A systematic review and meta-analysis to determine the effect of sperm DNA damage on in vitro fertilization and intracytoplasmic sperm injection outcome. Asian J Androl. 2017. PMID 27345006 · DOI · PMC5227680
- Osman A, Alsomait H, Seshadri S, El-Toukhy T, Khalaf Y. The effect of sperm DNA fragmentation on live birth rate after IVF or ICSI: a systematic review and meta-analysis. Reprod Biomed Online. 2015. PMID 25530036 · DOI
- McQueen DB, Zhang J, Robins JC. Sperm DNA fragmentation and recurrent pregnancy loss: a systematic review and meta-analysis. Fertil Steril. 2019. PMID 31056315 · DOI
- Wang YJ, Zhang RQ, Lin YJ, Zhang RG, Zhang WL. Relationship between varicocele and sperm DNA damage and the effect of varicocele repair: a meta-analysis. Reprod Biomed Online. 2012. PMID 22809864 · DOI
- Woerner SM, Benner A, Sutter C, Schiller M, Yuan YP, Keller G, et al.. Pathogenesis of DNA repair-deficient cancers: a statistical meta-analysis of putative Real Common Target genes. Oncogene. 2003. PMID 12700659 · DOI
- Li Z, Wang L, Cai J, Huang H. Correlation of sperm DNA damage with IVF and ICSI outcomes: a systematic review and meta-analysis. J Assist Reprod Genet. 2006. PMID 17019633 · DOI · PMC3455102
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.