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Cited by 62DNA Repair MechanismsEpigenetics and DNA MethylationGenomics and Chromatin Dynamics

Controlled DNA double-strand break induction in mice reveals post-damage transcriptome stability

Open access
Kim, Jeongkyu, Sturgill, David, Tran, Andy D., Sinclair, David A., Oberdoerffer, Philipp·2016·Nucleic Acids Research
DOI 10.1093/nar/gkv1482PMC PMC4838352
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Abstract

DNA double-strand breaks (DSBs) and their repair can cause extensive epigenetic changes. As a result, DSBs have been proposed to promote transcriptional and, ultimately, physiological dysfunction via both cell-intrinsic and cell-non-autonomous pathways. Studying the consequences of DSBs in higher organisms has, however, been hindered by a scarcity of tools for controlled DSB induction. Here, we describe a mouse model that allows for both tissue-specific and temporally controlled DSB formation at ∼140 defined genomic loci. Using this model, we show that DSBs promote a DNA damage signaling-dependent decrease in gene expression in primary cells specifically at break-bearing genes, which is reversed upon DSB repair. Importantly, we demonstrate that restoration of gene expression can occur independently of cell cycle progression, underlining its relevance for normal tissue maintenance. Consistent with this, we observe no evidence for persistent transcriptional repression in response to a multi-day course of continuous DSB formation and repair in mouse lymphocytes in vivo Together, our findings reveal an unexpected capacity of primary cells to maintain transcriptome integrity in response to DSBs, pointing to a limited role for DNA damage as a mediator of cell-autonomous epigenetic dysfunction.

Integrity signals

Registry

Crossref · 10.1093/nar/gkv1482

Cites

61 of 61 references verified0 citation errors · 0 not checkable

Statistics

Nothing to recompute.

Claims the paper makes

0 of 63 cited sources checked · 0 supported · 0 flagged

  • Findingown data

    33% of break-spanning DNA segments yielded a chimeric sequence joining one end of the I-PpoI-flanking DNA to a second polymorphic I-PpoI site about 1 Mb downstream.

    “However, 33% of break-spanning DNA segments yielded a chimeric DNA sequence, in which one end of the I-PpoI-flanking DNA was joined to that of a second, polymorphic I-PpoI site located ∼1 Mb downstream.”
    Quote in the paperSubstantial claim
  • Findingcitation

    No point mutations were detected at the I-PpoI DSB site after three days of induction.

    “In agreement with efficient, error-free religation of clean I-PpoI breaks, no point mutations were detected at the DSB site (40).”
    Quote in the paperSubstantial claim
  • Findingown data

    RNA-seq profiles showed a strong correlation between control and I-PpoI-expressing T cells.

    “Notably, RNA-seq profiles showed a strong correlation between control and I-PpoI-expressing T cells (Figure 3A), and the number of genes that were significantly altered upon I-PpoI induction was only moderately larger than the non-DSB-related variation observed between B cells from PpoSTOP; lck-Cre mice and lck-Cre controls (Figure 3B, Supplementary Table S3).”
    Quote in the paperSubstantial claim
  • Findingown data

    Gene expression can be restored after DSB repair without progression through the cell cycle.

    “Importantly, we demonstrate that restoration of gene expression can occur independently of cell cycle progression, underlining its relevance for normal tissue maintenance.”
    Quote in the paperSubstantial claim
  • Findingown data

    21% of genes altered in I-PpoI-expressing splenic T cells were also deregulated in thymic T cells (P < 10−4).

    “Remarkably, however, 21% of genes altered in I-PpoI-expressing T cells isolated from the spleen were also deregulated in the thymus (P < 10−4, Figure 3B).”
    Quote in the paperSubstantial claim
  • May combine two claims. 30
  • Classified as probably not a substantial claim. 21

  • May combine two claims.

    Findingown data

    All tested I-PpoI sites underwent DSB formation, with comparable cutting efficiencies for canonical and degenerate sites ranging from 10% to 20%.

    “All tested I-PpoI sites were subject to DSB formation, with comparable cutting efficiencies for canonical and degenerate sites ranging from 10% to 20% (Figure 2G, Supplementary Figure S2B, C).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingnone given

    I-PpoI sites are randomly distributed and occur at expected frequencies in genic and intergenic regions.

    “I-PpoI sites are distributed randomly, occurring with expected frequencies in genic and intergenic regions.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    The PpoSTOP allele allows efficient, temporally controlled and tissue-specific DSB induction in mice.

    “Together, these findings demonstrate that the PpoSTOP allele allows for efficient, temporally controlled and tissue-specific DSB induction in mice.”
    Quote in the paperSubstantial claim
    • Rests on an assumption: I-PpoI-mediated DSBs are representative of physiological DSBs for conclusions about the effects of DNA damage on the transcriptome.

  • May combine two claims.

    Findingown data

    Pathway analysis of the overlapping gene subset identified p53 signaling as the top overrepresented KEGG pathway (P = 8.5 × 10−5), and response to DNA damage stimulus and induction of apoptosis by intracellular signals as significantly enriched GO terms.

    “Pathway analysis of this subset revealed ‘p53 signaling’ (mmu04115) as the top overrepresented KEGG pathway (P = 8.5 × 10−5), and ‘response to DNA damage stimulus’ (GO:0006974) as well as ‘induction of apoptosis by intracellular signals’ (GO:0008629) as significantly enriched gene ontology terms (Figure 3A, Supplementary Table S4).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    No reduction in non-T cell numbers was detected in PpoSTOP; lck-Cre mice, consistent with T cell-specific DNA damage induction.

    “No reduction in non-T cell numbers was detected in PpoSTOP; lck-Cre mice, consistent with T cell-specific DNA damage induction (Figure 2B–E).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    No activation of DNA damage response genes was observed in splenic B cells from PpoSTOP; lck-Cre mice, and no significant overlap was detected between genes altered in B and T cells.

    “No activation of DNA damage response genes was observed in splenic B cells from PpoSTOP; lck-Cre mice and, accordingly, no significant overlap was detected between genes altered in B and T cells (Figure 3B, C, Supplementary Figure S3B).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    No aberrant junctions were observed in break-flanking DNA from lck-Cre controls, demonstrating that the distal fusions depend on I-PpoI.

    “No evidence for aberrant junctions was observed in break-flanking DNA from lck-Cre controls, demonstrating I-PpoI-dependent formation of these distal fusions (Figure 2H).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    In PpoSTOP/+; lck-Cre mice, GFP is expressed in about 40% of DN thymocytes and in over 90% of DP and CD4+ or CD8+ T cells, with no GFP+ cells in non-T lineage cells or lck-Cre controls.

    “Consistent with this, GFP expression was detected in ∼40% of PpoSTOP/+; lck-Cre DN thymocytes and reached > 90% in the more differentiated CD4/CD8 double-positive (DP) and CD4+ or CD8+ T cell subsets. No GFP+ cells were detected in non-T lineage cells or lck-Cre control mice (Figure 1D and data not shown).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    DSB induction results in relatively few gene expression changes in vivo, many of which are DDR-related.

    “These findings demonstrate that DSB induction results in relatively few gene expression changes in vivo, many of which are DDR-related.”
    Quote in the paperSubstantial claim
    • Rests on an assumption: The live cells that survive I-PpoI-induced DSBs are representative of the original cell population and are not selectively enriched for cells with stable transcriptomes.

  • May combine two claims.

    Findingown data

    In vitro, I-PpoI-proximal gene expression was lost, matching the in vivo findings.

    “In line with our in vivo findings, we observed a concomitant loss of I-PpoI-proximal gene expression.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Comparable reductions were seen for I-PpoI-induced breaks at rDNA, extending earlier in vitro results.

    “Similar results were observed for I-PpoI-induced DSBs at the rDNA, extending earlier in vitro findings (11) (Figure 3F).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
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  • May combine two claims.

    Findingown data

    In vitro DSB induction was as efficient as in vivo, cutting 15-20% of a given I-PpoI site and inducing γ-H2AX in about 60% of cells.

    “The efficiency of DSB induction in vitro was similar to that observed in vivo as measured by both I-PpoI site cutting (15–20% of a given site) and γ-H2AX induction (∼60% of cells)”
    Quote in the paperSubstantial claim

  • Classified as probably not a substantial claim. May combine two claims.

    Premisecitation

    Many DSB-induced chromatin changes, such as γ-H2AX phosphorylation, are restored to the pre-damage state after repair, leading to an access-repair-restore model of chromatin-directed DSB repair.

    “Many DSB-induced chromatin changes, such as the phosphorylation of histone H2AX (γ-H2AX), are restored to the pre-damage state once the break is repaired, which has led to an access (or prime)-repair-restore model of chromatin-directed DSB repair (8,9).”
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    Premisecitation

    Accumulation of DNA damage is a conserved hallmark of cancer and aging.

    “The accumulation of DNA damage is a conserved hallmark of cancer and aging (1).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [1] source

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  • May combine two claims.

    Interpretationown data

    Primary cells have an unexpected capacity to maintain transcriptome integrity after DSBs, suggesting DNA damage has a limited role in cell-autonomous epigenetic dysfunction.

    “Together, our findings reveal an unexpected capacity of primary cells to maintain transcriptome integrity in response to DSBs, pointing to a limited role for DNA damage as a mediator of cell-autonomous epigenetic dysfunction.”
    Quote in the paperSubstantial claim
    • Rests on an assumption: The live cells that survive I-PpoI-induced DSBs are representative of the original cell population and are not selectively enriched for cells with stable transcriptomes.

  • May combine two claims.

    Interpretationcitation

    The fraction of alleles that underwent DSB formation and repair is expected to be significantly greater than 33%, because proximal DSB ends join more efficiently than distant ones.

    “Given that the joining of proximal DSB ends is considerably more efficient than that of more distant ones (41), we expect the fraction of alleles that have undergone DSB formation and repair to be significantly greater than 33%.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [41] source

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    • Rests on an assumption: The chromosome 17 I-PpoI site is representative of other I-PpoI sites for assessing break/repair-associated mutagenesis.

  • Classified as probably not a substantial claim.

    Premisecitation

    DSB induction was sufficient to promote a subset of age-related pathologies in mice.

    “Consistent with the latter, DSB induction was found to be sufficient to promote a subset of age-related pathologies in mice (4).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [4] source

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  • May combine two claims.

    Premisecitation

    The mouse genome contains 19 canonical I-PpoI sites and at least 112 degenerate sites that are cut with comparable efficiency in vitro.

    “The mouse genome contains 19 bona fide I-PpoI sites and at least 112 degenerate sites that exhibit comparable I-PpoI-mediated cutting in vitro (27,28).”
    Quote in the paperSubstantial claim0 of 2 sources checked
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  • Classified as probably not a substantial claim. May combine two claims.

    Premisecitation

    DSBs cause significant changes in the chromatin environment at and beyond the break site, raising the possibility that DSB repair contributes to persistent epigenetic defects that may alter cell function.

    “In addition to the often detrimental effects of mutations and chromosomal abnormalities, DSBs cause significant changes in the chromatin environment both at and beyond the break site, raising the intriguing possibility that DSB repair contributes to (persistent) epigenetic defects that may eventually alter cell function (5).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [5] source

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  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    Defects in DSB repair can cause cell cycle arrest, apoptosis or genomic aberrations and have been linked to disease progression and premature aging phenotypes.

    “Defects in DSB repair can result in cell cycle arrest, apoptosis or genomic aberrations and have been linked to both disease progression and a premature onset of aging phenotypes (2,3).”
    Quote in the paperNot a substantial claim0 of 2 sources checked
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    Study design and conductown data

    I-PpoI-induced gene expression changes were validated for a subset of p53 target genes by quantitative RT-PCR.

    “I-PpoI-induced gene expression changes were validated for a subset of p53 target genes by quantitative RT-PCR (qRT-PCR).”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    DNA damage has been linked to redistribution of DNA repair-relevant chromatin modifiers to damage sites, which can cause epigenetic deregulation of undamaged genomic loci normally controlled by these proteins.

    “Beyond break-proximal chromatin reorganization, DNA damage has been linked to a redistribution of DNA repair-relevant chromatin modifiers to sites of damage, which can result in the epigenetic deregulation of ostensibly undamaged genomic loci normally controlled by these proteins (19).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [19] source

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  • May combine two claims.

    Interpretationown data

    The results indicate that persistent DSB formation and repair accompany a largely stable transcriptome in vivo, despite modest changes in DSB-bearing genes.

    “Together, these findings reveal that, although moderate transcriptional changes can be detected in DSB-bearing genes, persistent DSB formation and repair is associated with a surprisingly stable transcriptome in vivo.”
    Quote in the paperSubstantial claim

  • Classified as probably not a substantial claim.

    Premisecitation

    Prior work has shown that DSBs can disrupt expression of genes near breaks in cultured tumor cells.

    “DSBs were previously shown to interfere with the expression of break-proximal genes in tumor cell lines (11–13,42).”
    Quote in the paperSubstantial claim0 of 4 sources checked
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  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    DNA damage-driven inflammatory responses have been linked to aging in several organisms.

    “Indeed, DNA damage-driven inflammatory responses have been linked to aging in several organisms (4,21).”
    Quote in the paperNot a substantial claim0 of 2 sources checked
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  • Classified as probably not a substantial claim. May combine two claims.

    Premisecitation

    Recent findings demonstrate transcriptional repression in cis to DSBs that depends on DNA damage signaling and ceases after DSB repair is complete.

    “Consistent with this, recent findings demonstrate transcriptional repression in cis to DSBs, which depends on DNA damage signaling and ceases after DSB repair is complete (10–13).”
    Quote in the paperSubstantial claim0 of 4 sources checked
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  • Classified as probably not a substantial claim. May combine two claims.

    Premisecitation

    Epigenetic dysfunction in a small subset of cells may be sufficient to affect entire tissues and possibly organismal aging, as evidenced by the systemic impact of inflammatory cytokines from senescent cells.

    “It is of note that epigenetic dysfunction in a small subset of cells may be sufficient to affect entire tissues, and possibly organismal aging, as evidenced by the systemic impact of aberrantly expressed inflammatory cytokines derived from senescent cells (senescence-associated secretory phenotype) (20).”
    Quote in the paperSubstantial claim0 of 1 sources checked
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  • Classified as probably not a substantial claim.

    Premisecitation

    Persistent H2AX phosphorylation was observed in the absence of ongoing DNA damage in quiescent old hematopoietic stem cells.

    “Remarkably, persistent H2AX phosphorylation was recently observed in the absence of ongoing DNA damage in quiescent old hematopoietic stem cells (HSCs) (18).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [18] source

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  • May combine two claims.

    Premisecitation

    This prior work on transcriptional repression in cis to DSBs is limited to highly proliferative tumor cell lines, and its implications for animal tissues remain unclear.

    “This work is, however, limited to highly proliferative tumor cell lines, and its implications for animal tissues, which often exhibit little or no proliferation, remain unclear.”
    Quote in the paperSubstantial claim0 of 4 sources checked
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  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    A recent study found that age-associated functional decline from DNA damage is largely due to systemic effects of DSBs, such as cell death, tissue atrophy, and non-cell-autonomous inflammation.

    “a recent study shows that DNA damage-induced, age-associated functional decline can be attributed in large part to systemic consequences of DSBs, including cell death, tissue atrophy and the ensuing, non-cell-autonomous inflammatory response (4).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
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  • Classified as probably not a substantial claim. May combine two claims.

    Premisecitation

    γ-H2AX does not spread onto active genes, and transcription can be maintained accurately inside γ-H2AX domains.

    “the finding that γ-H2AX does not propagate on active genes and that transcription can be accurately maintained within γ-H2AX domains (49).”
    Quote in the paperSubstantial claim0 of 1 sources checked
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    Premisecitation

    DSBs are known to trigger dynamic reorganization of chromatin near breaks, which can affect expression of both nearby and apparently undamaged genes.

    “DSBs are known to promote a dynamic reorganization of break-proximal chromatin, with the potential to affect the expression of both break-proximal and ostensibly undamaged genes (10,13,19,45,48–50).”
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    Premisecitation

    Stochastic variation in gene expression in aged tissues is thought to contribute to age-associated organ decline even when tissue-wide expression is unchanged.

    “stochastic variations in gene expression in aged tissues are thought to be a contributing factor to age-associated organ decline even if gene expression across the tissue remains unaltered (59).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
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  • May combine two claims.

    Interpretationown data

    Restoration of DSB-induced expression changes can happen without proliferation, which rules out a specific need for S phase progression and, by extension, homology-directed repair.

    “we show here that the restoration of DSB-induced gene expression changes can occur in the absence of proliferation, ruling out a specific requirement for S phase progression and, by extension, homology-directed repair in this process.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Interpretationown data

    Although population-level expression was stable, the authors found DDR-dependent, transient repression of break-proximal genes in primary cells carrying DSBs.

    “Despite remarkably stable gene expression at the population level, we provide evidence for DDR-dependent, transient transcriptional repression of break-proximal genes in DSB-bearing primary cells (Figures 3D and 4F).”
    Quote in the paperSubstantial claim

  • Classified as probably not a substantial claim.

    Premisecitation

    Reducing ribosome subunits or interfering with the TOR/ribosomal protein S6 kinase pathway changes lifespan in many species, including mammals.

    “Depletion of ribosome subunits or interference with the target of rapamycin/ribosomal protein S6 kinase pathway, which functions to activate protein translation, were found to alter the lifespan of a variety of species including mammals (54–56).”
    Quote in the paperSubstantial claim0 of 3 sources checked
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    Premisecitation

    Replication stress has been reported to cause persistent rDNA-associated γ-H2AX foci and reduced rRNA/ribosome biogenesis in quiescent old HSCs.

    “it was recently reported that replication stress can result in the persistent formation of rDNA-associated γ-H2AX foci and a concomitant decrease in rRNA/ribosome biogenesis in quiescent old HSCs (18).”
    Quote in the paperSubstantial claim0 of 1 sources checked
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  • May combine two claims.

    Interpretationown data

    In primary cells, DSB-induced transcriptional changes are reversible/transient and require DDR activation.

    “Together, these findings demonstrate that DSB-induced transcriptional changes in primary cells are transient/reversible and depend on DDR activation.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Interpretationown data

    DSB repair is both necessary and sufficient for maintaining or restoring break-proximal gene expression and, by extension, epigenetic integrity in vivo.

    “Our findings further suggest that DSB repair is necessary and sufficient to ensure the maintenance and/or restoration of break-proximal gene expression profiles and, by extension, epigenetic integrity in vivo.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Several reports link ATM and DNA-PK to repressive chromatin formation and transcriptional silencing near DSBs.

    “The latter is in agreement with several reports implicating the DDR mediators ATM and DNA-PK in DSB-proximal repressive chromatin formation as well as transcriptional silencing (9–13,50).”
    Quote in the paperNot a substantial claim0 of 6 sources checked
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  • May combine two claims.

    Interpretationreasoning

    The findings suggest that most tissues can restore DSB-induced gene deregulation, though repair and silencing kinetics may vary with cell type and cell cycle state.

    “our findings, thus, suggest that most tissues have the potential to restore DSB-induced gene deregulation, although the kinetics of DSB repair and DNA damage-associated gene silencing may differ depending on cell type and/or cell cycle state.”
    Quote in the paperSubstantial claim0 of 4 sources checked
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  • Classified as probably not a substantial claim.

    Premisecitation

    Regulation of mRNA translation is a conserved mechanism controlling longevity.

    “the regulation of mRNA translation represents a conserved mechanism of longevity control (53).”
    Quote in the paperSubstantial claim0 of 1 sources checked
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  • Classified as probably not a substantial claim.

    Premisenone given

    It remains unclear how much DSBs contribute to epigenetic dysfunction in vivo.

    “However, the contribution of DSBs to epigenetic dysfunction in vivo remains unclear to date.”
    Quote in the paperSubstantial claim
43 of 43

  • The paper relies on this without support.

    There is a scarcity of tools for following the consequences of DSBs for cell and tissue function in higher organisms.

    “However, despite numerous cell-based reporter systems for DSB induction, there is a scarcity of tools to follow the consequences of DSBs for cell and tissue function in higher organisms.”

  • The paper relies on this without support.

    The live cells that survive I-PpoI-induced DSBs are representative of the original cell population and are not selectively enriched for cells with stable transcriptomes.

    “Analyses were limited to cells surviving I-PpoI-mediated DSB formation (live cells), and splenic B cells isolated from the same animals served as a negative control.”

  • The paper relies on this without support.

    The chromosome 17 I-PpoI site is representative of other I-PpoI sites for assessing break/repair-associated mutagenesis.

    “As a proxy for previous DSB formation and repair, we sequenced genomic DNA derived from an I-PpoI site on chromosome 17 to assess break/repair-associated mutagenesis following three days of I-PpoI induction.”

  • The paper relies on this without support.

    I-PpoI-mediated DSBs are representative of physiological DSBs for conclusions about the effects of DNA damage on the transcriptome.

    “To induce locally defined DSBs in mice, we took advantage of the fungal homing endonuclease I-PpoI.”
4 of 4

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • DNA damage can result in transient gene repression and stable gene expression changes observed in humans as young as 40.

    “DNA damage can result in transient gene repression (Kim et al., 2016) as well as more stable changes in gene expression that can be observed in humans as young as 40 years of age (Lu et al., 2004).”

    From The Aging Epigenome (2016) · cites this paper as Kim et al., 2016

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Related

Authors
Kim, J., Sturgill, D., Tran, A. D., Sinclair, D. A., & Oberdoerffer, P.
Affiliations
  • National Institutes of Health (US)
  • Harvard University (US)
Corresponding author
Oberdoerffer, Philipp
ORCID
Venue
Nucleic Acids Research
Publisher
Oxford University Press (OUP)
Published
2015-12-19
Volume
44
Issue
7
Pages
e64-e64
ISSN
  • 0305-1048 (ISSN-L)
  • 1362-4962
DOI
10.1093/nar/gkv1482
PMC
PMC4838352
OpenAlex
W2255462063
Semantic Scholar
8a3230b813445587595dbdfe00e592d6bede97f8
Cited by
62
References
61
Citations by year
2026: 2 · 2025: 6 · 2024: 4 · 2023: 8 · 2022: 6 · 2021: 8 · 2020: 6 · 2019: 6 · 2018: 1 · 2017: 9 · 2016: 6
FWCI
2.31
Type
journal article
Language
en
Open access
Licence
public-domain
Locations
  • Nucleic Acids Research (publishedVersion, public-domain)
  • PubMed Central (publishedVersion, public-domain)
  • PubMed (publishedVersion)
  • Digital Access to Scholarship at Harvard (DASH) (Harvard University) (submittedVersion, cc-by)
  • HighWire Press Open Archive (submittedVersion)
Funders
  • National Institutes of Health
  • National Institute on Aging (R37AG028730, P01AG027916, R01AG028730, R01AG019719, R01AG019972, R13AG033466)
  • National Institute of General Medical Sciences (R01GM068072)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA Repair Mechanisms
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
Keywords
DNA double-strand breaks, DNA double-strand break repair, DNA damage signaling, transcriptional repression, mouse model, primary cells, lymphocytes, cell cycle independence, gene expression recovery
MeSH terms
Animals, Cells, Cultured, Endodeoxyribonucleases, Mice, Transgenic, Signal Transduction, Mice, DNA Breaks, Double-Stranded, Genetic Loci, Transcriptome

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Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Claims read by deepseek-v4.1-flash under definition version 3 (extract-v3) on 2026-10-06.

Classified by jev-1.13-20260917 (gold-guideline-v0.2) on 2026-10-06.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

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