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 (730 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 reaction that severs one of the covalent sugar-phosphate linkages between nucleotides that compose the sugar phosphate backbone of DNA. It is catalyzed enzymatically, chemically or by radiation. Cleavage may be exonucleolytic - removing the end nucleotide, or endonucleolytic - splitting the strand in two.
Definition: NLM Medical Subject Headings (MeSH) scope note (Public domain (U.S. National Library of Medicine); attribution requested). View the MeSH record.
Where it fits in the MeSH classification
- Broader topics
- Biochemical Phenomena; Genetic Phenomena
Related concepts
Research landscape
PubMed indexes 2,118 records tagged with the MeSH heading “DNA Cleavage” (counts retrieved 2026-10-29). 451 of them (21.3%) were published from 2020 onward, and the busiest period so far is 2010-2019 with 1,450 records.
Reviews account for 71 records (3.4%) and meta-analyses for 0. Randomized controlled trials number 0 (0.0%) 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 | 257 |
| 2010-2019 | 1,450 |
| 2020 onward | 451 |
Publication-type chart data
| Type | Records | Share |
|---|---|---|
| Reviews | 71 | 3.4% |
| Meta-analyses | 0 | 0.0% |
| Randomized controlled trials | 0 | 0.0% |
Method: PubMed query "DNA Cleavage"[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 |
|---|---|---|---|---|
| Efficient precise knockin with a double cut HDR donor after CRISPR/Cas9-mediated double-stranded DNA cleavage | 2017 | Research article Design not recorded in structured metadata | 402 | cc by PMID 28219395 · DOI · PMC5319046 |
| Tight nuclear tethering of cGAS is essential for preventing autoreactivity | 2019 | Research article Design not recorded in structured metadata | 271 | cc by PMID 31808743 · DOI · PMC6927687 |
| A conformational checkpoint between DNA binding and cleavage by CRISPR-Cas9 | 2017 | Research article Design not recorded in structured metadata | 249 | cc by PMID 28808686 · DOI · PMC5547770 |
| Rapid DNA cleavage by the LINE-1 endonuclease proximal to DNA ends and at mismatches | 2026 | Research article Design not recorded in structured metadata | 3 | cc by PMID 41325800 · DOI · PMC12809410 |
Efficient precise knockin with a double cut HDR donor after CRISPR/Cas9-mediated double-stranded DNA cleavage [1]
Abstract reading summary — source excerpts
- Opening excerpt
- BackgroundPrecise genome editing via homology-directed repair (HDR) after double-stranded DNA (dsDNA) cleavage facilitates functional genomic research and holds promise for gene therapy.
- Closing excerpt
- ConclusionsTaken together, these findings provide guidance for the design of HDR donor vectors and the selection of HDR-enhancing factors for applications in genome research and precision medicine.
- 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 (176 words)
BackgroundPrecise genome editing via homology-directed repair (HDR) after double-stranded DNA (dsDNA) cleavage facilitates functional genomic research and holds promise for gene therapy. However, HDR efficiency remains low in some cell types, including some of great research and clinical interest, such as human induced pluripotent stem cells (iPSCs).ResultsHere, we show that a double cut HDR donor, which is flanked by single guide RNA (sgRNA)-PAM sequences and is released after CRISPR/Cas9 cleavage, increases HDR efficiency by twofold to fivefold relative to circular plasmid donors at one genomic locus in 293 T cells and two distinct genomic loci in iPSCs. We find that a 600 bp homology in both arms leads to high-level genome knockin, with 97-100% of the donor insertion events being mediated by HDR. The combined use of CCND1, a cyclin that functions in G1/S transition, and nocodazole, a G2/M phase synchronizer, doubles HDR efficiency to up to 30% in iPSCs.ConclusionsTaken together, these findings provide guidance for the design of HDR donor vectors and the selection of HDR-enhancing factors for applications in genome research and precision medicine.
Abstract reproduced from the open-access article under the recorded cc by licence; © the authors. PMID 28219395 · DOI · PMC5319046
Tight nuclear tethering of cGAS is essential for preventing autoreactivity [2]
Abstract reading summary — source excerpts
- Opening excerpt
- cGAS is an intracellular innate immune sensor that detects double-stranded DNA.
- Closing excerpt
- Thus, tight nuclear tethering maintains the resting state of cGAS and prevents autoreactivity.
- 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)
cGAS is an intracellular innate immune sensor that detects double-stranded DNA. The presence of billions of base pairs of genomic DNA in all nucleated cells raises the question of how cGAS is not constitutively activated. A widely accepted explanation for this is the sequestration of cGAS in the cytosol, which is thought to prevent cGAS from accessing nuclear DNA. Here, we demonstrate that endogenous cGAS is predominantly a nuclear protein, regardless of cell cycle phase or cGAS activation status. We show that nuclear cGAS is tethered tightly by a salt-resistant interaction. This tight tethering is independent of the domains required for cGAS activation, and it requires intact nuclear chromatin. We identify the evolutionarily conserved tethering surface on cGAS and we show that mutation of single amino acids within this surface renders cGAS massively and constitutively active against self-DNA. Thus, tight nuclear tethering maintains the resting state of cGAS and prevents autoreactivity.
Abstract reproduced from the open-access article under the recorded cc by licence; © the authors. PMID 31808743 · DOI · PMC6927687
A conformational checkpoint between DNA binding and cleavage by CRISPR-Cas9 [3]
Abstract reading summary — source excerpts
- Opening excerpt
- The Cas9 endonuclease is widely used for genome engineering applications by programming its single-guide RNA, and ongoing work is aimed at improving the accuracy and efficiency of DNA targeting.
- Closing excerpt
- Sequence mismatches between the DNA target and guide RNA prevent transitions from the checkpoint intermediate to the active conformation, providing selective avoidance of DNA cleavage at stably bound off-target sites.
- 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)
The Cas9 endonuclease is widely used for genome engineering applications by programming its single-guide RNA, and ongoing work is aimed at improving the accuracy and efficiency of DNA targeting. DNA cleavage of Cas9 is controlled by the conformational state of the HNH nuclease domain, but the mechanism that governs HNH activation at on-target DNA while reducing cleavage activity at off-target sites remains poorly understood. Using single-molecule Förster resonance energy transfer, we identified an intermediate state of Streptococcus pyogenes Cas9, representing a conformational checkpoint between DNA binding and cleavage. Upon DNA binding, the HNH domain transitions between multiple conformations before docking into its active state. HNH docking requires divalent cations, but not strand scission, and this docked conformation persists following DNA cleavage. Sequence mismatches between the DNA target and guide RNA prevent transitions from the checkpoint intermediate to the active conformation, providing selective avoidance of DNA cleavage at stably bound off-target sites.
Abstract reproduced from the open-access article under the recorded cc by licence; © the authors. PMID 28808686 · DOI · PMC5547770
Rapid DNA cleavage by the LINE-1 endonuclease proximal to DNA ends and at mismatches [4]
Abstract reading summary — source excerpts
- Opening excerpt
- Long interspersed element 1 (LINE-1, L1) is a eukaryotic retrotransposon that propagates through an RNA intermediate.
- Closing excerpt
- Together, these results indicate that EN cleavage is based primarily on DNA structure rather than sequence, that many L1 insertion attempts likely fail after cleavage at the priming step , and that mismatches and possibly other DNA conformational alterations promote EN cleavage, broadening our understanding of the genomic impact of L1.
- 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 (252 words)
Long interspersed element 1 (LINE-1, L1) is a eukaryotic retrotransposon that propagates through an RNA intermediate. Its mutagenic insertion mechanism, target-primed reverse transcription (TPRT), requires coordinated activities of the encoded ORF2 protein (ORF2p) endonuclease (EN) and reverse transcriptase (RT) domains. EN initiates TPRT by nicking target genomic DNA, creating a 3'-OH that primes ORF2p RT for complementary DNA synthesis using the bound L1 RNA template. L1 insertions occur preferentially at 5'-TTTTT↓AA consensus motifs; this bias could reflect site-specific EN cleavage or sequence requirements in the subsequent RT priming step, in which the cut genomic DNA flap must base pair with the poly(A) RNA template. We find that, in vitro, EN is promiscuous, cutting linear DNA oligonucleotides and plasmids at many non-consensus sites. We discovered a cleavage activity on a mismatched substrate that was nicked ∼40-fold faster than duplex DNA containing the consensus site and identify three features promoting rapid cutting. First, EN cleaves two nucleotides downstream of mismatches, favoring A-G mismatches or T•G/U•G wobble pairs. Second, both mismatch and consensus sequences are cleaved >2-fold faster when proximal to a DNA end. Third, end-proximal EN cutting depends on end composition: 5' overhangs cut fastest, followed by 3' overhangs, followed by blunt ends. Together, these results indicate that EN cleavage is based primarily on DNA structure rather than sequence, that many L1 insertion attempts likely fail after cleavage at the priming step , and that mismatches and possibly other DNA conformational alterations promote EN cleavage, broadening our understanding of the genomic impact of L1.
Abstract reproduced from the open-access article under the recorded cc by licence; © the authors. PMID 41325800 · DOI · PMC12809410
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 Natural and engineered nicking endonucleases--from cleavage mechanism to engineering of strand-specificity [5]
- Research article DNA Topoisomerase Inhibitors: Trapping a DNA-Cleaving Machine in Motion [6]
- Research article Using CRISPR-Cas systems as antimicrobials [7]
- Research article Making the cut(s): how Cas12a cleaves target and non-target DNA [8]
- Research article Type III CRISPR-Cas systems: when DNA cleavage just isn't enough [9]
- Research article DNA binding, photocleavage, and topoisomerase inhibition of functionalized ruthenium(II)-polypyridine complexes [10]
References
- Zhang JP, Li XL, Li GH, Chen W, Arakaki C, Botimer GD, et al.. Efficient precise knockin with a double cut HDR donor after CRISPR/Cas9-mediated double-stranded DNA cleavage. . 2017. PMID 28219395 · DOI · PMC5319046
- Volkman HE, Cambier S, Gray EE, Stetson DB. Tight nuclear tethering of cGAS is essential for preventing autoreactivity. . 2019. PMID 31808743 · DOI · PMC6927687
- Dagdas YS, Chen JS, Sternberg SH, Doudna JA, Yildiz A. A conformational checkpoint between DNA binding and cleavage by CRISPR-Cas9. . 2017. PMID 28808686 · DOI · PMC5547770
- Miller BD, Smail BA, Van Eeuwen T, Kodama H, Kondo K, Jiang H, et al.. Rapid DNA cleavage by the LINE-1 endonuclease proximal to DNA ends and at mismatches. . 2026. PMID 41325800 · DOI · PMC12809410
- Chan SH, Stoddard BL, Xu SY. Natural and engineered nicking endonucleases--from cleavage mechanism to engineering of strand-specificity. Nucleic Acids Res. 2011. PMID 20805246 · DOI · PMC3017599
- Bax BD, Murshudov G, Maxwell A, Germe T. DNA Topoisomerase Inhibitors: Trapping a DNA-Cleaving Machine in Motion. J Mol Biol. 2019. PMID 31301408 · DOI · PMC6723622
- Bikard D, Barrangou R. Using CRISPR-Cas systems as antimicrobials. Curr Opin Microbiol. 2017. PMID 28888103 · DOI
- Swarts DC. Making the cut(s): how Cas12a cleaves target and non-target DNA. Biochem Soc Trans. 2019. PMID 31671185 · DOI
- Pyenson NC, Marraffini LA. Type III CRISPR-Cas systems: when DNA cleavage just isn't enough. Curr Opin Microbiol. 2017. PMID 28865392 · DOI
- Gao F, Chao H, Ji LN. DNA binding, photocleavage, and topoisomerase inhibition of functionalized ruthenium(II)-polypyridine complexes. Chem Biodivers. 2008. PMID 18972534 · DOI
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.
See how EvidenceLib is built. Spotted an error? Email support@evidencehelix.com.
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.