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Cited by 283Telomeres, Telomerase, and SenescenceGenomics and Chromatin DynamicsGenetics, Aging, and Longevity in Model Organisms

Senescence-associated heterochromatin foci are dispensable for cellular senescence, occur in a cell type- and insult-dependent manner and follow expression of p16ink4a

Open access
Kosar, Martin, Bartkova, Jirina, Hubackova, Sona, Hodny, Zdenek, Lukas, Jiri, Bartek, Jiri·2011·Cell Cycle
DOI 10.4161/cc.10.3.14707
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Abstract

Cellular senescence, an irreversible proliferation arrest evoked by stresses such as oncogene activation, telomere dysfunction, or diverse genotoxic insults, has been implicated in tumor suppression and aging. Primary human fibroblasts undergoing oncogene-induced or replicative senescence are known to form senescence-associated heterochromatin foci (SAHF), nuclear DNA domains stained densely by DAPI and enriched for histone modifications including lysine9-trimethylated histone H3. While cellular senescence occurs also in premalignant human lesions, it is unclear how universal is SAHF formation among various cell types, under diverse stresses, and whether SAHF occur in vivo. Here, we report that human primary fibroblasts (BJ and MRC-5) and primary keratinocytes undergoing replicative senescence, or premature senescence induced by oncogenic H-Ras, diverse chemotherapeutics and bacterial cytolethal distending toxin, show differential capacity to form SAHF. Whereas all tested cell types formed SAHF in response to activated H-Ras, only MRC-5, but not BJ fibroblasts or keratinocytes, formed SAHF under senescence induced by etoposide, doxorubicin, hydroxyurea, bacterial intoxication or telomere attrition. In addition, DAPI-defined SAHF were detected on paraffin sections of Ras-transformed cultured fibroblasts, but not human lesions at various stages of tumorigenesis. Overall, our results indicate that unlike the widely present DNA damage response marker γH2AX, SAHF is not a common feature of cellular senescence. Whereas SAHF formation is shared by diverse cultured cell types under oncogenic stress, SAHF are cell-type-restricted under genotoxin-induced and replicative senescence. Furthermore, while the DNA/DAPI-defined SAHF formation in cultured cells parallels enhanced expression of p16(ink4a) , such 'prototypic' SAHF are not observed in tissues, including premalignant lesions, irrespective of enhanced p16(ink4a) and other features of cellular senescence.

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Registry

Crossref · 10.4161/cc.10.3.14707

Cites

61 of 61 references verified0 citation errors · 0 not checkable

Statistics

Nothing to recompute.

Claims the paper makes

0 of 32 cited sources checked · 0 supported · 0 flagged

  • Findingown data

    The percentage of SAHF-positive cells remained unchanged during extended culture up to 250 days after oncogene transduction.

    “Of note, the proportions of SAHF-positive cells did not change during extended periods of cultivation until 250 days after oncogene transduction.”
    Quote in the paperNot a substantial claim
  • Findingown data

    Lentiviral delivery of H-Ras V12 caused widespread senescence in BJ fibroblasts, MRC-5 fibroblasts, and primary keratinocytes by day 12, based on morphology, SA-β-Gal staining, and reduced BrdU incorporation.

    “In time course experiments, lentiviral transduction of H-Ras V12 led in all three cell types to widespread cellular senescence by day 12 after transduction, as judged by changes in morphology, enhanced SA-β-Gal staining (Fig. 1) and grossly diminished DNA replication indicated by inhibited incorporation of BrdU (Sup.Table 1).”
    Quote in the paperSubstantial claim
  • Findingown data

    MRC-5 cells undergoing senescence showed increased p16ink4a in all six scenarios, though at different levels.

    “In contrast to BJ cells, and consistent with the degree of SAHF formation, extracts of MRC-5 cells undergoing senescence showed increased p16 ink4a in all six scenarios, albeit to different levels.”
    Quote in the paperSubstantial claim
  • Findingown data

    Frozen colorectal adenoma sections showed no clear evidence of classical DNA/DAPI-defined SAHF despite variable and partly focal expression of HP1γ, H3K9Me3, and SA-β-gal activity.

    “Consistent with the data obtained on paraffin sections, no clear evidence of the classical DNA/DAPI-defined SAFH was seen upon examination of these adenoma frozen sections, despite the positive variable and partly even focal, expression pattern of the heterochromatin markers HP1γ, H3K9Me3 and SA-β-gal activity (data not shown and Sup.Material reviewed in ref. 48).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [48]

      Not checked in the free run.

  • Findingown data

    The ability to form senescence-associated heterochromatin foci closely correlated with increased levels of p16ink4a in this study.

    “the close correlation of the ability to form SAHF and the increased level of p16 ink4a”
    Quote in the paperNot a substantial claim
  • May combine two claims. 22
  • The quote only partly states this claim. 1
  • Classified as probably not a substantial claim. 10

  • May combine two claims.

    Findingown data

    The earliest SAHF were detected at day 5 in all three cell types, and MRC-5 had the highest initial percentage of positive cells.

    “The first detectable SAHF appeared at day 5 in all three cell types, with the highest percentage of the initially positive cells seen in MRC-5 (Fig. 2A).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    By day 12, the initial differences among the three cell types in the proportion of SAHF-positive cells had become minimized, with no statistically significant differences.

    “The initial differences in relative proportions of SAHF-positive cells among the three cell types became minimized by day 12, however, when no statistically significant differences in percentages of SAHFpositive cells were found (Fig. 2A).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    The highest p16ink4a abundance in MRC-5 occurred after Ras exposure, and the lowest after doxorubicin exposure.

    “Notably, the highest and lowest abundance of p16 ink4a were found in MRC-5 senescent after Ras and doxorubicin exposure, respectively (Fig. 6A).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    Drug-induced senescence was accompanied by SAHF formation only in MRC-5 cells, not in BJ cells or keratinocytes treated with any of the three drugs.

    “In contrast to consistent heterochromatinization and SAHF formation during the Ras oncogene-induced senescence in all three cell types, drug-induced senescence was accompanied by SAHF formation only in MRC-5 cells, but not in BJ or keratinocytes treated with any of the three drugs (Figs. 2 and 3).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    In senescent BJ cells, robust p16ink4a induction occurred only under Ras-induced senescence, the only condition with classical DNA/DAPI-defined SAHF.

    “Specifically, in cell extracts of senescent BJ cells, robust induction of p16 ink4a was only apparent under Ras-induced senescence, the only condition associated with the occurrence of classical DNA/DAPI-defined SAHF in these cells.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Under senescence caused by etoposide, doxorubicin, hydroxyurea, bacterial intoxication, or telomere attrition, only MRC-5 formed SAHF; BJ fibroblasts and keratinocytes did not.

    “Whereas all tested cell types formed SAHF in response to activated H-Ras, only MRC-5, but not BJ fibroblasts or keratinocytes, formed SAHF under senescence induced by etoposide, doxorubicin, hydroxyurea, bacterial intoxication or telomere attrition.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Old senescent MRC-5 populations had DAPI-stained SAHF foci along with other senescence features, whereas senescent BJ fibroblasts lacked SAHF.

    “Interestingly, the 'old,' senescent populations of MRC-5 cells displayed DAPI-stained DNA/SAHF foci accompanying other features of senescence in contrast to lack of SAHF formation in senescent BJ fibroblasts (Fig. 4B and D) despite the fact that both strains shared other recognized features of the senescent phenotype and the fact that the BJ cells reached the senescent state after more passages in”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    BJ cells reached replicative senescence after more passages in vitro than MRC-5 cells.

    “despite the fact that both strains shared other recognized features of the senescent phenotype and the fact that the BJ cells reached the senescent state after more passages in vitro compared to MRC-5.”
    Quote in the paperNot a substantial claim

  • May combine two claims. The quote only partly states this claim.

    Findingown data

    DAPI-defined SAHF that colocalized with H3K9Me3 and HP1γ were seen in HdCDT-exposed senescent MRC-5 cells but not in similarly treated BJ cells or keratinocytes.

    “Formation of DAPI-defined SAHF that colocalized with heterochromatin markers H3K9Me3 and HP1γ was observed in HdCDT-exposed senescent MRC-5 cells but not in similarly treated BJ cells and”
    Quote in the paperSubstantial claim

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

    Premisecitation

    SAHF have been implicated in transcriptional silencing of proliferation-promoting genes.

    “functionally SAHF have been implicated in transcriptional silencing of proliferationpromoting genes.4”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [4]

      Not checked in the free run.

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

    Premisecitation

    Activated Ras oncogene and bacterial intoxication are known triggers of premature senescence.

    “premature senescence induced by activated Ras oncogene, 22 bacterial intoxication 42 and several genotoxic chemotherapeutics”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [22]

      Not checked in the free run.

    • cites [42]

      Not checked in the free run.

  • May combine two claims.

    Interpretationown data

    SAHF formation is not a universal component of the senescence program and appears dispensable for multiple modes of cellular senescence in various cell types.

    “First, our data strongly indicate that SAHF formation is not a universal component of the senescence program and, in fact, appears to be dispensable for multiple modes of cellular senescence, in various cell types.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Interpretationown data

    SAHF formation under several genotoxic drugs is restricted to only one of the three normal human cell types tested.

    “We conclude that unlike the universal occurrence of SAHF in oncogene-induced senescence, SAHF formation is restricted to only one of the three normal human cell types undergoing senescence evoked by several genotoxic drugs.”
    Quote in the paperSubstantial claim

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

    Premisecitation

    γH2AX and other functional markers of activated DNA damage response can be conveniently assessed on tissue sections.

    “γH2AX and other functional markers of activated DDR can conveniently be assessed on tissue sections.13,48,[53][54][55]”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites [13]

      Not checked in the free run.

    • cites [48]

      Not checked in the free run.

    • cites [53]

      Not checked in the free run.

  • May combine two claims.

    Interpretationown data

    The capacity to form SAHF does not necessarily track the senescent state in replicative and toxin-evoked senescence, and MRC-5 cells are more prone to SAHF formation than other normal cell types including epithelial cells.

    “Collectively, these experiments further support the notion that the ability to form SAHF does not necessarily correlate with the senescent state, here documented for replicative and toxinevoked senescence, and that the MRC-5 cells are more prone to SAHF formation compared to other normal cell types including epithelial cells.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation

    HdCDT induces cellular senescence in subpopulations of various normal and cancer-derived human cell types.

    “a scenario that we recently reported to induce cellular senescence in the subpopulations of various human cell types, both normal and cancer-derived”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [42]

      Not checked in the free run.

  • May combine two claims.

    Interpretationown data

    Proliferating cancer cells do not form classical DNA/DAPI-defined SAHF, which are apparently distinct from H3K9Me3/HP1γ-rich heterochromatin domains.

    “Furthermore, the data also show that unlike senescent, arrested cells, the proliferating cancer cells do not form the classical DNA/DAPIdefined SAHF, which are apparently distinct from the H3K9Me3/HP1γ-rich heterochromatin domains that do not necessarily reflect silencing of proliferation genes such as cyclin A, a protein highly expressed in all cell lines of our panel (data not shown).”
    Quote in the paperSubstantial claim

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

    Premisecitation

    Cellular senescence in clinical specimens of premalignant human lesions is accompanied by enhanced H3K9Me3 and HP1γ heterochromatinization markers correlated with active DNA damage signaling.

    “We have previously reported that cellular senescence observed in clinical specimens of premalignant human lesions is accompanied by enhanced heterochromatinization markers H3K9Me3 and HP1γ that correlated with active DNA damage signaling.48”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [48]

      Not checked in the free run.

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

    Premisecitation

    Several chemotherapeutic drugs, including etoposide, hydroxyurea, and doxorubicin, are known to induce premature senescence in human cells.

    “Several chemotherapeutic drugs including etoposide, 43 hydroxyurea 44 and doxorubicin 45,46 are known to induce premature senescence in human cells.”
    Quote in the paperNot a substantial claim0 of 4 sources checked
    • cites [43]

      Not checked in the free run.

    • cites [44]

      Not checked in the free run.

    • cites [45]

      Not checked in the free run.

    • cites [46]

      Not checked in the free run.

  • May combine two claims.

    Interpretationown data

    SAHF formation is shared by diverse cultured cell types under oncogenic stress but is cell-type-restricted under genotoxin-induced and replicative senescence.

    “Whereas SAHF formation is shared by diverse cultured cell types under oncogenic stress, SAHF are cell-type-restricted under genotoxin-induced and replicative senescence.”
    Quote in the paperSubstantial claim

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

    Study design and conductnone given

    Diagnoses were independently verified by two experienced pathologists according to World Health Organization classification criteria.

    “The diagnoses were independently verified by two experienced pathologists according to the established criteria of classification recommended by the World Health Organization.”
    Quote in the paperNot a substantial claim

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

    Study design and conductown data

    Alpha-tubulin was used as a loading control to ensure equal protein loading.

    “Alpha-tubulin was used as a marker to ensure equal loading.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Interpretationcitation

    In replicative senescence, arrest mediated by p16ink4a seems more robust and irreversible even when p53 is depleted, whereas arrest under low p16ink4a conditions may be partially reversible.

    “the p16 ink4a -mediated senescence-associated proliferation arrest appears to be more robust and irreversible even upon depletion of p53, as compared to the possibly partially reversible arrest under p16 ink4a -low conditions, at least in replicative senescence.32”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [32]

      Not checked in the free run.

  • Classified as probably not a substantial claim.

    Study design and conductnone given

    Identical image acquisition parameters were used for quantitative and comparative imaging.

    “For quantitative and comparative imaging, identical image acquisition parameters were used.”
    Quote in the paperSubstantial claim

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

    Study design and conductnone given

    All samples were originally collected at university hospitals in Aarhus and Copenhagen under ethical approval from a local Medical Research Ethics Committee in Denmark.

    “All samples were originally collected at the University hospitals in Aarhus and Copenhagen, under ethical approval received from a local Medical Research Ethics Committee in Denmark.”
    Quote in the paperNot a substantial claim

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

    Study design and conductown data

    The results presented are averages with 95% confidence intervals, tested by unpaired t-test, from a minimum of three independent experiments.

    “The results shown are averages (with 95% confidence interval, tested by unpaired t-test) of a minimum of three independent experiments.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Interpretationcitation

    p16ink4a is critical for the formation of senescence-associated heterochromatin foci, robust engagement of pRb, and irreversible cell cycle arrest, although it is not essential for every mode of cellular senescence.

    “The overall picture emerging is that p16 ink4a , albeit not essential for every mode of cellular senescence, is critical for the formation of SAHF, 4 robust engagement of pRb and irreversible cell cycle arrest, 62,63”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites [4]

      Not checked in the free run.

    • cites [62]

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    • cites [63]

      Not checked in the free run.

  • May combine two claims.

    Interpretationreasoning

    Low p16ink4a expression shifts senescence induction toward greater reliance on the p53-p21 axis and possibly other mechanisms, likely including DNA damage checkpoints, only some of which require p53.

    “It appears that in cells with low expression of p16 ink4a , senescence induction relies more on the p53-p21 axis, and possibly other mechanisms, likely including also DNA damage checkpoints, only some of which require p53.”
    Quote in the paperNot a substantial claim
28 of 28

  • The paper relies on this without support.

    p16ink4a protein abundance reflects activation of the p16ink4a-pRb pathway in the cells studied.

    “we argued that the observed differences might reflect variable levels of the p16 ink4a CDK inhibitor, and hence the activation of the pRb pathway, whose role in SAHF formation has been documented.4,38”
1 of 1

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?

  • p16 induction is robust in response to oncogenic stimuli, even in cells that undergo replicative senescence with low p16 levels.

    “At the same time, p16 induction is robust in response to oncogenic stimuli, even in cells that undergo replicative senescence with low p16 levels [52].”

    From Mechanisms and Regulation of Cellular Senescence (2021) · cites this paper as [52]

  • SAHF formation is not a universal feature of senescence.

    “However, SAHF formation is not a universal feature of senescence.”

    From Mechanisms and Regulation of Cellular Senescence (2021) · cites this paper as [52]

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

Each contradiction between two passages listed here was confirmed by an independent check.

  • The bacterial-intoxication citation points to a drug study

    Minor

    Reference 42 is cited for a previously described mode of senescence induced by bacterial intoxication, but its listed article concerns DNA-damage-induced senescence in tumor cells.

  • Error bars are described as both confidence intervals and standard deviations

    Minor

    The statistics section says the results are shown with 95% confidence intervals, but the Figure 2 legend says its error bars show standard deviations. These are different measures of variability.

  • Holotoxin-preparation citations do not match the listed papers

    Minor

    The methods attribute preparation of the bacterial toxin subunits and holotoxin to references 47 and 75. The listed entries concern a tumorigenesis barrier and H2AX phosphorylation, respectively, rather than that preparation.

  • Reference 48 does not match the cited earlier study

    Minor

    The text attributes an earlier study of heterochromatin markers in premalignant lesions to reference 48. The listed reference 48 is instead a study of BMI-1026-induced SAHF formation by different authors.

4 of 4

Cites

Flagged first, then by citations

Research works printed but not linked: 18

  1. Narita M, Nunez S, Heard E, Lin AW, Hearn SA, Spector DL, et al. Rb-mediated heterochromatin for- mation and silencing of E2F target genes during cel- lular senescence. Cell 2003; 113:703-16.
  2. Kuilman T, Michaloglou C, Vredeveld LC, Douma S, van Doorn R, Desmet CJ, et al. Oncogene-induced senescence relayed by an interleukin-dependent inflam- matory network. Cell 2008; 133:1019-31.
  3. Sedelnikova OA, Horikawa I, Zimonjic DB, Popescu NC, Bonner WM, Barrett JC. Senescing human cells and ageing mice accumulate DNA lesions with unre- pairable double-strand breaks. Nat Cell Biol 2004; 6:168-70.
  4. d'Adda di Fagagna F, Reaper PM, Clay-Farrace L, Fiegler H, Carr P, Von Zglinicki T, et al. A DNA dam- age checkpoint response in telomere-initiated senes- cence. Nature 2003; 426:194-8.
  5. Gray-Schopfer VC, Cheong SC, Chong H, Chow J, Moss T, Abdel-Malek ZA, et al. Cellular senescence in naevi and immortalisation in melanoma: a role for p16? Br J Cancer 2006; 95:496-505.
  6. Brenner AJ, Stampfer MR, Aldaz CM. Increased p16 expression with first senescence arrest in human mam- mary epithelial cells and extended growth capacity with p16 inactivation. Oncogene 1998; 17:199-205.
  7. Bringold F, Serrano M. Tumor suppressors and onco- genes in cellular senescence. Exp Gerontol 2000; 35:317-29.
  8. Halazonetis TD, Gorgoulis VG, Bartek J. An onco- gene-induced DNA damage model for cancer develop- ment. Science 2008; 319:1352-5.
  9. Goodarzi AA, Noon AT, Jeggo PA. The impact of het- erochromatin on DSB repair. Biochem Soc Trans 2009; 37:569-76.
  10. Guerra L, Teter K, Lilley BN, Stenerlow B, Holmes RK, Ploegh HL, et al. Cellular internalization of cyto- lethal distending toxin: A new end to a known pathway. Cell Microbiol 2005; 7:921-34.
  11. Adams PD. Remodeling of chromatin structure in senescent cells and its potential impact on tumor sup- pression and aging. Gene 2007; 397:84-93.
  12. Di Micco R, Fumagalli M, Cicalese A, Piccinin S, Gasparini P, Luise C, et al. Oncogene-induced senes- cence is a DNA damage response triggered by DNA hyper-replication. Nature 2006; 444:638-42.
  13. Passos JF, Saretzki G, von Zglinicki T. DNA damage in telomeres and mitochondria during cellular senes- cence: Is there a connection? Nucleic Acids Res 2007; 35:7505-13.
  14. Chen Z, Trotman LC, Shaffer D, Lin HK, Dotan ZA, Niki M, et al. Crucial role of p53-dependent cellular senescence in suppression of Pten-deficient tumorigen- esis. Nature 2005; 436:725-30.
  15. Collado M, Gil J, Efeyan A, Guerra C, Schuhmacher AJ, Barradas M, et al. Tumour biology: Senescence in premalignant tumours. Nature 2005; 436:642.
  16. Blagosklonny MV. Aging-suppressants: Cellular senes- cence (hyperactivation) and its pharmacologic decelera- tion. Cell Cycle 2009; 8:1883-7.
  17. Chen QM, Bartholomew JC, Campisi J, Acosta M, Reagan JD, Ames BN. Molecular analysis of H 2 O 2 - induced senescent-like growth arrest in normal human fibroblasts: p53 and Rb control G 1 arrest but not cell replication. Biochem J 1998; 332:43-50.
  18. Lobrich M, Shibata A, Beucher A, Fisher A, Ensminger M, Goodarzi AA, et al. gammaH2AX foci analy- sis for monitoring DNA double-strand break repair: strengths, limitations and optimization. Cell Cycle 2010; 9:662-9.

Cited by

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Related

Authors
Kosar, M., Bartkova, J., Hubackova, S., Hodny, Z., Lukas, J., & Bartek, J.
Affiliations
Danish Cancer Society (DK)
Venue
Cell Cycle
Publisher
Informa UK Limited
Published
2011-02
Volume
10
Issue
3
Pages
457-468
ISSN
  • 1538-4101 (ISSN-L)
  • 1551-4005
DOI
10.4161/cc.10.3.14707
OpenAlex
W2083176422
Semantic Scholar
815d4c31d4f348034a5d35051dd2bd5e4c9b9f36
Cited by
283
References
61
Citations by year
2026: 4 · 2025: 8 · 2024: 8 · 2023: 14 · 2022: 13 · 2021: 20 · 2020: 17 · 2019: 15 · 2018: 17 · 2017: 21 · 2016: 29 · 2015: 27 · 2014: 23 · 2013: 30 · 2012: 27
FWCI
19.63
Type
journal article
Language
en
Open access
Locations
  • Cell Cycle (publishedVersion)
  • PubMed (publishedVersion)
  • ASEP (submittedVersion, public-domain)
  • Zenodo (CERN European Organization for Nuclear Research) (submittedVersion, other-oa)
Funders
  • European Commission
  • National Research Foundation
  • Danmarks Grundforskningsfond
  • Grantová Agentura České Republiky (GAP301/10/1525, AV 0Z5039906, GA301/08/0353)
  • Novo Nordisk
Topics
  • Health Sciences › Medicine › Physiology › Telomeres, Telomerase, and Senescence
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
Keywords
cellular senescence, senescence-associated heterochromatin foci, replicative senescence, oncogene-induced senescence, p16INK4a, genotoxic stress, telomere shortening, cytolethal distending toxin, keratinocytes, fibroblasts, precancerous lesions, histone H3K9 trimethylation, tumor suppression
MeSH terms
Bacterial Toxins, Cell Line, DNA Damage, Heterochromatin, Humans, Genes, ras, Cellular Senescence, Cyclin-Dependent Kinase Inhibitor p16, Cell Proliferation

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