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Cited by 300Telomeres, Telomerase, and SenescenceCancer-related Molecular PathwaysGenetics, Aging, and Longevity in Model Organisms

Senescence from G2 arrest, revisited

Open access
Gire, Véronique, Dulić, Vjekoslav·2015·Cell Cycle
DOI 10.1080/15384101.2014.1000134PMC PMC4353294
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Abstract

Senescence was classically defined as an irreversible cell cycle arrest in G1 phase (G1 exit) triggered by eroded telomeres in aged primary cells. The molecular basis of this G1 arrest is thought to be due to a DNA damage response, resulting in accumulation of the cyclin dependent kinase (Cdk) inhibitors p21 and p16 that block the inactivating phosphorylation of the retinoblastoma tumor suppressor pRb, thereby preventing DNA replication. More than a decade ago, several studies showed that p21 also mediates permanent DNA damage-induced cell cycle arrest in G2 (G2 exit) by inhibiting mitotic Cdk complexes and pRb phosphorylation. The idea that the senescence program can also be launched after G2 arrest has gained support from several recent publications, including evidence for its existence in vivo.

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Crossref · 10.1080/15384101.2014.1000134

Cites

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Claims the paper makes

0 of 98 cited sources checked · 0 supported · 0 flagged

  • Premisecitation

    The ATM/p53/p21 pathway triggered by telomere erosion or activated oncogenes has a central role in senescence-associated G1 arrest.

    “Like in proliferating cells exposed to DNA damage, 32,33 the ATM/ p53/p21 pathway triggered by telomere erosion or activated oncogenes plays a central role in senescence-associated G1 arrest (Fig. 1).”
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    • cites [33] Waldman T, 1995, Cancer Res

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  • Premisecitation

    Senescence is increasingly viewed as an early defense against tumor development by preventing proliferation of cells with damaged DNA.

    “Senescence is increasingly considered to be an essential early line of defense against tumor development by preventing proliferation of cells with damaged DNA, [10][11][12]”
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  • Premisenone given

    Senescent cells are found in pre-cancerous lesions in mice and humans but not in later malignant stages.

    “Moreover, senescent cells are observed in pre-cancerous lesions in mice and in humans, but not in the subsequent malignant stages.”
    Quote in the paperSubstantial claim
  • Premisecitation
    § Senescence from G2 arrest, revisited

    p21 also mediates permanent DNA damage-induced G2 arrest by inhibiting mitotic Cdk complexes and pRb phosphorylation.

    “More than a decade ago, several studies showed that p21 also mediates permanent DNA damage-induced cell cycle arrest in G2 (G2 exit) by inhibiting mitotic Cdk complexes and pRb phosphorylation.”
    Quote in the paperSubstantial claim
  • Premisecitation

    p21 blocks the inactivating phosphorylation of pRb by Cdk2 and Cdk4/6, a key mechanism in the senescence program.

    “In addition to directly preventing DNA replication by inhibiting Cdk2, p21 also blocks the inactivating phosphorylation of pRb by Cdk2 and Cdk4/6 (Fig. 1), which is a key mechanism in the senescence program.39”
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  • Classified as probably not a substantial claim. 26

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    Premisecitation

    Absence of pRb phosphorylation, presence of G1 cyclins, and lack of mitotic cyclins are an early-recognized hallmark of senescence.

    “Indeed, absence of pRb phosphorylation, 40 together with the presence of G1 cyclins (cyclins D1 and E1) 27 and the lack of mitotic cyclins (cyclin B1), 41 is an early-recognized hallmark of senescence.”
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    Premisecitation

    Continuous Cdk-mediated inactivation of pRb family proteins is required for cell cycle progression because active pocket proteins sequester E2F factors and repress replication and division genes.

    “Continuous Cdk-mediated inactivation of pRb family proteins is a prerequisite for cell cycle progression, because active (hypo-phosphorylated) pocket-proteins drive cell cycle exit by sequestering E2F family transcription factors and repressing the genes required for DNA replication and cell division.3”
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    Premisecitation

    Senescence has also been implicated in promoting carcinogenesis and age-related pathologies through the senescence-associated secretory phenotype.

    “However, senescence has also been implicated both in promoting carcinogenesis 15 and in age-related pathologies 16,17 through its autocrine and paracrine effects, known as the senescence-associated secretory phenotype (SASP) originally described by the Campisi group.18,19”
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    Premisecitation

    Activated DNA damage response markers occur in many pre-cancerous lesions, and checkpoint-compromising mutations are suggested to be required for tumor progression.

    “Indeed, the markers of activated DDR are found in many pre-cancerous lesions, and mutations compromising DNA damage checkpoint (for example, defects in ATM/p53 pathway) are suggested to be a prerequisite for tumor progression.13,14”
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    Premisecitation

    Senescence was originally defined as an irreversible G1-phase arrest.

    “Originally, cellular senescence was defined as an irreversible arrest in the G1 phase of the cell cycle (reviewed in refs.25,26 ).”
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    Premisenone given

    p53 induces p21, which is an essential mediator of senescence.

    “Following activation by panoply of stress signals, p53 induces the expression of the Cdk inhibitor p21 Waf1/Cip1 (p21), an essential mediator of senescence (see below).”
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    Premisecitation

    p53 is a major target of ATM and ATR and has a pivotal role in the DNA damage response.

    “p53 (TP53), which is a major target of the PI3K-related protein kinases (PI3K) ATM and ATR and that plays a pivotal role in DDR 5”
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    Premisecitation

    mTOR has been implicated in senescence, linking cell growth to p53 and DNA damage response pathways.

    “More recently, mTOR (mechanistic target of rapamycin), another member of the PI3K family that controls cell growth in response to nutritional cues, has also been implicated in senescence, thus linking cellular growth with the p53 and DDR pathways.[6][7][8][9]”
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    Premisecitation

    SASP factors can reinforce cell-cycle arrest cell autonomously and can influence surrounding cells and immune surveillance non-cell autonomously, leading to elimination of senescent cells.

    “SASP factors can act cell autonomously by reinforcing cell-cycle arrest and non-cell autonomously by influencing cells in the surrounding environment and promoting immune surveillance, leading to the elimination of senescent cells.20,12”
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    Premisereasoning

    Genotoxic agents can induce senescence by triggering DNA damage response pathways and cell cycle checkpoints that halt proliferation.

    “Senescence can be also induced by genotoxic agents, which like eroded telomeres or hyperactive oncogenes, trigger the DNA damage response (DDR) pathways and activate cell cycle checkpoints to halt proliferation.”
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    Premisecitation

    Cellular senescence was originally described as an irreversible arrest in G1 phase.

    “Originally, cellular senescence was defined as an irreversible arrest in the G1 phase of the cell cycle (reviewed in refs.25,26 ).”
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    Premisenone given
    § Senescence from G2 arrest, revisited

    The G1 arrest of senescence is thought to result from a DNA damage response that raises p21 and p16, which block pRb phosphorylation and prevent DNA replication.

    “The molecular basis of this G1 arrest is thought to be due to a DNA damage response, resulting in accumulation of the cyclin dependent kinase (Cdk) inhibitors p21 and p16 that block the inactivating phosphorylation of the retinoblastoma tumor suppressor pRb, thereby preventing DNA replication.”
    Quote in the paperNot a substantial claim

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    Premisecitation

    p16 is not required for the cell cycle arrest of replicative senescence; its late induction after p21-mediated arrest was suggested to stabilize rather than induce the senescent state.

    “Unlike p21, p16 is not required for cell cycle arrest associated with replicative senescence, and its late induction, which occurs only after p21-mediated cell cycle arrest, was suggested to stabilize rather than induce the senescent state.28,42,[48][49][50]”
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    Interpretationcitation

    The distribution of senescent cells is consistent with the idea that senescence limits early tumor progression and that malignancy involves escaping senescence.

    “This is consistent with the hypothesis that senescence restricts tumor progression during the early stages of tumorigenesis, whereas progression to malignancy would involve evading senescence. 1”
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    Interpretationcitation

    Senescent cells are not merely non-dividing bystanders; their active metabolism can produce pro- or anti-tumorigenic effects depending on the microenvironment.

    “Therefore, senescent cells are not merely non-dividing bystanders but, due to their active metabolism (reviewed in ref. 8 ), they can elicit pro-and/or anti-tumorigenic responses, depending on the microenvironment.12”
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    Premisecitation

    Cellular senescence is a permanent cell cycle arrest with distinct metabolic activity and marked morphological changes.

    “Cellular senescence is a state of permanent cell cycle arrest characterized by distinct metabolic activity and dramatic changes in cell morphology.1,2”
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    Premisecitation

    Mutations, silencing, or loss of CDKN2A facilitate senescence bypass and are frequently associated with carcinogenesis.

    “In agreement with p16's role as a guardian of senescence, mutations, silencing or loss of CDKN2A, the gene encoding p16, facilitate senescence bypass and it is frequently associated with carcinogenesis (reviewed in.51,52”
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    Premisereasoning

    p21 was proposed to be paramount for G2 exit because it completely and irreversibly inhibits cyclin B1-Cdk1, preventing activation by CAK, PLK1, or Cdc25 phosphatases.

    “This mechanism was proposed to be paramount for cell cycle exit in G2 because, unlike transient inhibition of Cdk1 activation through the Chk1/2 pathway, p21 completely and irreversibly inhibits cyclin B1-Cdk1 complexes, thus rendering impossible their activation by CAK, PLK1 or Cdc25 phosphatases (Fig. 2).”
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    Premisecitation

    Premature p21-dependent APC/C-Cdh1 activation in G2-arrested cells was thought to result from Emi1 downregulation, although a Cdc14B role was not formally excluded.

    “This premature and p21-dependent activation of APC/C-Cdh1 in G2arrested cells was thought to be due to down-regulation of the APC/C inhibitor Emi1, 74 although an implication of the Cdc14B phosphatase in this process was not formally excluded.77”
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    Premisecitation

    p16 is dispensable for mitotic skipping and senescence induction but is required for senescence maintenance.

    “The finding that p16 is dispensable both for mitotic skipping and induction of senescence, but is required for its maintenance, is in full agreement with the models proposed earlier whereby p21 is a major mediator of irreversible cell cycle arrest.28,49”
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    Premisecitation

    DNA damage signaling from partial telomere deprotection is insufficient to fully activate the ATM-mediated G2/M checkpoint; after mitosis, DNA damage induces p53-dependent G1 exit.

    “In agreement with this hypothesis, a recent report showed that, unlike genomic breaks, DNA damage signaling elicited by partial telomere deprotection is insufficient to fully activate the ATM-mediated G2/M checkpoint.83 Instead, after completion of mitosis, DNA damage induces p53-dependent cell cycle exit in G1.”
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    Premisecitation

    DNA damage-induced G2 arrest is triggered by ATM/ATR-activated Chk1/2, which inhibit Cdc25 phosphatases that activate cyclin B1-Cdk1.

    “According to the prevailing model, 56 DNA damage-induced G2 arrest is triggered by the ATM/ATR-activated checkpoint kinases Chk1/2 that inhibit Cdc25 phosphatases, which are activators of the key mitotic regulator, cyclin B1-Cdk1 (Fig. 2).”
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    Premisecitation

    In non-transformed cells, DNA damage-induced Chk2 phosphorylation at Thr68 is very transient and is not the best indicator of Chk2 activation.

    “It should be noted that, at least in non-transformed cells, DNA damage-induced Chk2 phosphorylation at Thr68 is very transient 72 and hence not the best indicator of Chk2 activation (as opposed to SDS-PAGE shift).”
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    Premisecitation

    Recent publications have confirmed earlier observations and added evidence for a G2 exit program and its role in senescence.

    “Several recent publications have confirmed these old observations and provided additional evidence supporting the existence of a G2 exit program and its role in senescence.”
    Quote in the paperSubstantial claim

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    Premisecitation

    APC/C-Cdh1 activation alone is not sufficient to induce senescence; repression of mitotic regulators by pRb family pocket proteins is also required.

    “However, unlike p53-mediated mitotic bypass, APC/C Cdh1 activation alone does not appear to be sufficient to induce senescence, that additionally requires repression of mitotic regulators by pRb family pocket proteins (Fig. 2).”
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    Interpretationcitation

    The G2 exit program was proposed to act as a safeguard preventing adaptation to the G2 checkpoint and passage of damaged cells into mitosis.

    “Based on these findings, it was proposed that the “G2 exit program” might serve as a safeguard mechanism to prevent cell adaptation to the G2 checkpoint and consequently the passage into mitosis of cells with damaged DNA (Fig. 2; 59 ).”
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  • May combine two claims.

    Premisecitation

    Downregulation of mitotic regulators after G2 arrest is due both to pRb-mediated suppression and to protein degradation by APC/C-Cdh1.

    “Originally, downregulation of mitotic regulators following G2 arrest was attributed to pRb-mediated suppression of their expression 64 (Fig. 2).However, subsequent work in several laboratories provided evidence that this is also due to protein degradation triggered by anaphase-promoting complex/cyclosome (APC/C) and its co-activator Cdh1 [74][75][76] (Fig. 2).”
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    Premisecitation

    In aging cells, telomeric DNA damage persists at a subset of the shortest telomeres and fully activates the DNA damage response, unlike functional telomeres that trigger a transient protective response in G2.

    “Unlike functional telomeres that trigger a transient DNA damage response in G2 that is required for their protection, 82 telomeric DNA damage in aging cells persists at a subset of the shortest telomeres and fully activates DDR.81”
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    Premisereasoning

    G2-arrested fibroblasts with p53 or pRb compromised by viral oncogenes fail to exit permanently and continue expressing mitotic regulators after prolonged genotoxic exposure.

    “G2arrested fibroblasts, in which either p53 or pRb was compromised by viral oncogenes, failed to permanently exit the cell cycle and expressed mitotic regulators even after prolonged exposure to genotoxic agents.”
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    Premisecitation

    Tetraploidization triggered by permanently damaged telomeres promotes tumorigenic transformation of mouse cells.

    “Subsequent work by the same team has shown that tetraploidization triggered by permanently damaged telomeres promotes tumorigenic transformation of mouse cells. 92”
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    Premisecitation

    A model proposes that cells stably blocked in G2 undergo mitotic bypass into tetraploid G1, where p21-mediated inhibition of cyclin E1-Cdk2 prevents replication.

    “A model originally proposed by the Lahav group suggests that cells stably blocked in G2 eventually undergo mitotic bypass -a passage from G2 to G1 without chromosome segregation -and enter a tetraploid G1 phase where they cannot replicate due to p21-mediated inhibition of cyclin E1-Cdk2.89”
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    Premisecitation

    Prolonged ICRF-193 exposure in normal human fibroblasts causes p53/p21-dependent irreversible G2 exit, with reduced cyclin A and B1 and accumulation of non-phosphorylated pRb family pocket proteins.

    “Prolonged exposure to this drug led to p53/p21dependent irreversible cell cycle exit in G2 that was associated with down-regulation of both cyclin A and cyclin B1 and accumulation of non-phosphorylated pRb family pocket proteins.59”
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    Interpretationcitation

    Chk2 does not appear essential for G2 arrest; damaged cells more likely progress into mitosis because of inefficient Chk1 activation and/or weak p21 induction.

    “A major caveat of this interpretation is that Chk2 does not seem to play an essential role in G2 arrest 84,85,72 and it is more likely that damaged cells progress into mitosis due to inefficient Chk1 activation 86 and/or lack of robust p21 induction.”
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    Premisecitation

    Replicative senescence or various senescence-causing stimuli induce p53-dependent mitotic bypass, irreversible arrest in 4N G1, and accumulation of p16 and beta-galactosidase.

    “The Nakanishi group showed that replicative senescence or exposure to various senescence-causing stimuli induces p53-dependent mitotic bypass (referred to as mitotic skipping), entailing irreversible cell cycle arrest in the 4N G1 state and accumulation of the senescent markers p16 and b-galactosidase.93”
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    Premisenone given

    Telomere dysfunction, oncogene hyperactivity, and several DNA-damaging agents activate the ATM/ATR DNA damage response pathway.

    “Dysfunctional telomeres, hyperactive oncogenes and various genotoxic agents stimulate the ATM/ATRmediated DNA damage response (DDR) pathway.”
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    Premisenone given

    ATM phosphorylates the p53 tumor suppressor.

    “ATM also phosphorylates the p53 tumor suppressor that, by inducing the Cdk inhibitor p21 Waf1/Cip1 (p21), plays a central role in the G1 exit program (late response).”
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    Interpretationcitation

    A more likely explanation is that p16 compensates for p21 loss by blocking pRb phosphorylation by cyclin D1-Cdk4/6, supporting a role for the p16-pRb pathway in senescence maintenance.

    “While this hypothesis cannot be entirely dismissed, a more likely explanation is that p16 might compensate for the absence of p21 in blocking pRb phosphorylation by cyclin D1-Cdk/6 (Fig. 1 and Fig. 2), thus justifying the proposed role of the p16-pRb pathway in senescence maintenance.”
    Quote in the paperSubstantial claim

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    Premisecitation

    In U2OS cells, p21 induction is impaired by an inefficient ATM response and probably by a Wip1 phosphatase mutation that interferes with p53 activation.

    “In this p53/pRb proficient cell line, p21 induction is impaired due to inefficient ATM response 72 and, probably, mutation of the Wip1 phosphatase that interferes with p53 activation.97”
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    Interpretationcitation

    Strong persistent DNA damage signaling from POT1a/b double knockdown likely causes sustained Chk1/2 activation that prevents Cdk1 activation and mitosis, producing prolonged G2 arrest that enables mitotic bypass and a new replication round.

    “The most likely explanation is that the strong and persistent DNA damage signaling induced by POT1a/b double knockdown 88 causes sustained Chk1/2 activation that prevents Cdk1 activation (and mitosis), resulting in prolonged G2 arrest.This would enable the mitotic bypass and the onset of a new round of replication (Fig. 3).”
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    Premisenone given

    Cyclin D1-Cdk4/6 complexes phosphorylate and inactivate pRb family pocket proteins.

    “In addition to cyclin E1-Cdk2 (cE1-K2) complexes, p21 also inhibits cyclin D1-Cdk4/6 (cD1-K4/6) complexes that phosphorylate and inactivate pRb family pocket proteins.”
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    Premisenone given

    Senescence is associated with p16 upregulation.

    “Senescence is also associated with p16 Ink4A (p16) upregulation, but the pathways leading to its induction are not entirely elucidated.”
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    Interpretationnone given

    Recent publications have emphasized the importance of the G2 exit program in senescence.

    “In conclusion, a flurry of papers in the last 2 y has highlighted the relevance of the G2 exit program in senescence.”
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    Premisenone given

    p16 specifically targets Cdk4/6.

    “This Cdk inhibitor specifically targets Cdk4/6 and prevents their association with D-type cyclins.”
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  • Classified as probably not a substantial claim.

    Premisecitation

    p21 depletion prevents senescence less efficiently than p53 depletion.

    “Moreover, p21 depletion prevents senescence less efficiently than p53 depletion, prompting the authors to suggest that p53 might activate the pRb family independently of p21 (Fig. 5G in ref. 93 ).”
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    Premisenone given

    Cyclin E1-Cdk2 is a key regulator of the G1/S transition.

    “The ATM/ATR kinases induce the early response by activating Chk1/2 checkpoint kinases that, in turn, by inhibiting Cdc25 phosphatases, prevent activation of cyclin E1-Cdk2, which is a key regulator of G1/S transition.”
    Quote in the paperSubstantial claim

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    Premisecitation

    Transient p53 induction in G2, but not G1, is sufficient to induce mitotic bypass and senescence; this is not true for p21.

    “While the previously discussed works 93,95 show that transient induction of p53 in G2 (but not in G1) is sufficient to induce mitotic bypass and senescence, this is not the case for p21.93”
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    Premisenone given

    Cdc25 phosphatases promote mitosis by activating cyclin B1-Cdk1 complexes.

    “The early response involves Chk1/2-mediated inhibition of Cdc25 phosphatases, which promote mitosis by activating cyclin B1-Cdk1 complexes (cB1/K1).”
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    Interpretationcitation

    4N senescent cells occur in human melanocyte naevi, suggesting that the G2 exit program has a more general role in senescence.

    “Importantly, this work also provided evidence for the occurrence of 4N senescent cells in human melanocyte naevi, the first in vivo senescence model, 94 suggesting that the G2 exit program has a more general role in senescence.”
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    Premisecitation

    Mitotic bypass requires p53; its absence leads to aberrant mitosis and cell death.

    “The results showing that mitotic bypass requires p53, as its absence leads to aberrant mitosis and cell death, corroborate the observations by the Karlseder team, 83 but they apparently contradict the finding that mitotic bypass in p53-deficient cells leads to endoreplication.88”
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    Premisenone given

    p16 prevents Cdk4/6 association with D-type cyclins.

    “This Cdk inhibitor specifically targets Cdk4/6 and prevents their association with D-type cyclins.”
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    Premisecitation

    In old cells lacking p53 and pRb, severe telomere shortening causes crisis, widespread death, and tetraploidization via endoreplication or failed mitosis.

    “Similarly, in aging p53/pRbdeficient cells, extensive telomere erosion induces crisis with massive cell death and tetraploidization through endoreplication or mitotic failure.92”
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    Premisenone given

    p21 activates pRb by blocking Cdk-mediated pRb phosphorylation.

    “Like in G1 arrest, p21 also activates pRb by blocking Cdk-mediated pRb phosphorylation.”
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    Premisecitation

    These cells then progress into mitosis and eventually die.

    “In the absence of sustained Chk1/2 activation, p53/p21-deficient cells exposed to genotoxic agents arrest only transiently in G2 and then progress into mitosis and eventually die.59,93”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [59] source

      Not checked in the free run.

    • cites [93] source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based).

    Interpretationnone given

    p16 likely maintains senescence in G2 by acting on pRb kinases.

    “Like in G1 arrest, p16 stabilizes senescence in G2 presumably by targeting pRb kinases.”
    Quote in the paperNot a substantial claim
54 of 54

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?

  • Senescent cells may also stop in G2 to block mitosis in the presence of DNA damage.

    “Senescent cells may also stop in G2 to block mitosis in the presence of DNA damage [32] (Figure 1).”

    From Mechanisms and Regulation of Cellular Senescence (2021) · cites this paper as [32]

  • Unscheduled degradation of mitotic regulators is believed to result in cell cycle exit in G2.

    “Their unscheduled degradation is believed to result in cell cycle exit in G2 [32].”

    From Mechanisms and Regulation of Cellular Senescence (2021) · cites this paper as [32]

Cites

Flagged first, then by citations

Research works printed but not linked: 4

  1. Waldman T, 1995, Cancer Res, 55, 5187
  2. Sandhu C, 2000, Cancer Res, 60, 2616
  3. Levedakou EN, 1995, Cancer Res, 55, 2500
  4. Andreassen PR, 2001, Cancer Res, 61, 7660

Cited by

Sorted by citations

Authors
Gire, V., & Dulić, V.
Affiliations
Centre National de la Recherche Scientifique (FR)
Corresponding author
Dulić, Vjekoslav
ORCID
Venue
Cell Cycle
Publisher
Informa UK Limited
Published
2015-02-01
Volume
14
Issue
3
Pages
297-304
ISSN
  • 1538-4101 (ISSN-L)
  • 1551-4005
DOI
10.1080/15384101.2014.1000134
PMC
PMC4353294
OpenAlex
W1536843121
Semantic Scholar
8b9deb6f2b2b47e41e32f456120981b29be98434
Cited by
300
References
97
Citations by year
2026: 21 · 2025: 33 · 2024: 47 · 2023: 32 · 2022: 31 · 2021: 24 · 2020: 27 · 2019: 31 · 2018: 24 · 2017: 16 · 2016: 11 · 2015: 3
Type
journal article
Language
en
Open access
Locations
  • Cell Cycle (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
  • HAL (submittedVersion)
Topics
  • Health Sciences › Medicine › Physiology › Telomeres, Telomerase, and Senescence
  • Health Sciences › Medicine › Oncology › Cancer-related Molecular Pathways
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
Keywords
cellular senescence, G2 cell cycle arrest, DNA damage response, p21, p16, retinoblastoma protein, cyclin-dependent kinase inhibitors, telomere shortening, cell cycle arrest
MeSH terms
Animals, Humans, Models, Biological, Signal Transduction, G1 Phase, Cellular Senescence, Cell Proliferation, G2 Phase Cell Cycle Checkpoints

About these checks

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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