The DOI matches its Crossref record; 61 of the 61 references it cites were found in a registry or an index; none of the 32 sources its claims cite is checked for support yet.
Senescence-associated heterochromatin foci are dispensable for cellular senescence, occur in a cell type- and insult-dependent manner and follow expression of p16ink4a
Open accessAbstract
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.
Overview
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
0 of 32 cited sources checked · 0 supported · 0 flagged
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Of note, the proportions of SAHF-positive cells did not change during extended periods of cultivation until 250 days after oncogene transduction.”
§ Senescence-associated heterochromatin foci are dispensable for cellular senescence, occur in a cell type-and insult-dependent manner and follow expression of p16 ink4a > SAHF formation is common in oncogene-induced senescence.
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesA result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“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).”
§ Senescence-associated heterochromatin foci are dispensable for cellular senescence, occur in a cell type-and insult-dependent manner and follow expression of p16 ink4a > SAHF formation is common in oncogene-induced senescence.
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesA result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“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.”
§ Senescence-associated heterochromatin foci are dispensable for cellular senescence, occur in a cell type-and insult-dependent manner and follow expression of p16 ink4a > SAHF formation is common in oncogene-induced senescence.
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIn the paper
“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).”
§ Senescence-associated heterochromatin foci are dispensable for cellular senescence, occur in a cell type-and insult-dependent manner and follow expression of p16 ink4a > SAHF formation is common in oncogene-induced senescence.
What the sources say
- Not checked yetcites [48]
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesA result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“the close correlation of the ability to form SAHF and the increased level of p16 ink4a”
§ Senescence-associated heterochromatin foci are dispensable for cellular senescence, occur in a cell type-and insult-dependent manner and follow expression of p16 ink4a > Discussion
Strength:plain· not yet calibratedCausal:correlational· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesA result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“As can be seen from the examples of Ras-transformed BJ fibroblasts, immunohistochemical examination of paraffin sections still revealed the DNA/DAPI-defined SAHF in such specimens (Fig. 5A), albeit at somewhat lower frequency compared to senescent BJ cells grown and analyzed directly on coverslips (Fig. 1).”
§ Senescence-associated heterochromatin foci are dispensable for cellular senescence, occur in a cell type-and insult-dependent manner and follow expression of p16 ink4a > SAHF formation is common in oncogene-induced senescence.
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesA result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“In contrast to sections from paraffin embedded Ras-transformed BJ cells, no SAHF formation was observed on tissue sections of normal epithelial tissues, adenomas or carcinomas (Fig. 5B and data not shown).”
§ Senescence-associated heterochromatin foci are dispensable for cellular senescence, occur in a cell type-and insult-dependent manner and follow expression of p16 ink4a > SAHF formation is common in oncogene-induced senescence.
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesA result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“This differential SAHF formation was not altered even when the experiments were prolonged until day 21 of keratinocytes (Fig. 4A and C and data not shown)”
§ Senescence-associated heterochromatin foci are dispensable for cellular senescence, occur in a cell type-and insult-dependent manner and follow expression of p16 ink4a > SAHF formation is common in oncogene-induced senescence.
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesA result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“we did find elevated γH2AX in all three cell types, and under senescence induced by all six stimuli studied here”
§ Senescence-associated heterochromatin foci are dispensable for cellular senescence, occur in a cell type-and insult-dependent manner and follow expression of p16 ink4a > Discussion
Strength:plain· not yet calibratedCausal:correlational· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesA result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Overall, the proportion of SAHF-positive cells among the drug-induced MRC-5 senescent cells was lower (approx.20%) than in oncogene-induced MRC-5 senescent cells, despite a similar overall senescent phenotype was seen in settings with distinct senescenceinducing stimuli (Figs. 2 and 3, Sup.Table 1 and Sup.Fig. 1).”
§ Senescence-associated heterochromatin foci are dispensable for cellular senescence, occur in a cell type-and insult-dependent manner and follow expression of p16 ink4a > SAHF formation is common in oncogene-induced senescence.
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes
- It may state two separate claims as one. 22
- The quote only partly states this claim. 1
- Probably not a substantial claim. 10
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“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).”
§ Senescence-associated heterochromatin foci are dispensable for cellular senescence, occur in a cell type-and insult-dependent manner and follow expression of p16 ink4a > SAHF formation is common in oncogene-induced senescence.
Strength:plain· not yet calibratedCausal:correlational· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“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).”
§ Senescence-associated heterochromatin foci are dispensable for cellular senescence, occur in a cell type-and insult-dependent manner and follow expression of p16 ink4a > SAHF formation is common in oncogene-induced senescence.
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Notably, the highest and lowest abundance of p16 ink4a were found in MRC-5 senescent after Ras and doxorubicin exposure, respectively (Fig. 6A).”
§ Senescence-associated heterochromatin foci are dispensable for cellular senescence, occur in a cell type-and insult-dependent manner and follow expression of p16 ink4a > SAHF formation is common in oncogene-induced senescence.
Strength:plain· not yet calibratedCausal:correlational· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“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).”
§ Senescence-associated heterochromatin foci are dispensable for cellular senescence, occur in a cell type-and insult-dependent manner and follow expression of p16 ink4a > SAHF formation is common in oncogene-induced senescence.
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“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.”
§ Senescence-associated heterochromatin foci are dispensable for cellular senescence, occur in a cell type-and insult-dependent manner and follow expression of p16 ink4a > SAHF formation is common in oncogene-induced senescence.
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“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.”
§ Senescence-associated heterochromatin foci are dispensable for cellular senescence, occur in a cell type-and insult-dependent manner and follow expression of p16 ink4a > Introduction
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“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”
§ Senescence-associated heterochromatin foci are dispensable for cellular senescence, occur in a cell type-and insult-dependent manner and follow expression of p16 ink4a > SAHF formation is common in oncogene-induced senescence.
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“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.”
§ Senescence-associated heterochromatin foci are dispensable for cellular senescence, occur in a cell type-and insult-dependent manner and follow expression of p16 ink4a > SAHF formation is common in oncogene-induced senescence.
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“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”
§ Senescence-associated heterochromatin foci are dispensable for cellular senescence, occur in a cell type-and insult-dependent manner and follow expression of p16 ink4a > SAHF formation is common in oncogene-induced senescence.
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one. The quote only partly states this claim.
In the paper
“functionally SAHF have been implicated in transcriptional silencing of proliferationpromoting genes.4”
§ Senescence-associated heterochromatin foci are dispensable for cellular senescence, occur in a cell type-and insult-dependent manner and follow expression of p16 ink4a > SAHF formation is common in oncogene-induced senescence.
What the sources say
- Not checked yetcites [4]
Strength:hedged· not yet calibratedCausal:correlational· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
None of the sources cited for this claim have been checked yet.
In the paper
“premature senescence induced by activated Ras oncogene, 22 bacterial intoxication 42 and several genotoxic chemotherapeutics”
§ Senescence-associated heterochromatin foci are dispensable for cellular senescence, occur in a cell type-and insult-dependent manner and follow expression of p16 ink4a > Introduction
What the sources say
- Not checked yetcites [22]
- Not checked yetcites [42]
Strength:boosted· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“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.”
§ Senescence-associated heterochromatin foci are dispensable for cellular senescence, occur in a cell type-and insult-dependent manner and follow expression of p16 ink4a > SAHF formation is common in oncogene-induced senescence.
Load-bearingStrength:hedged· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“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.”
§ Senescence-associated heterochromatin foci are dispensable for cellular senescence, occur in a cell type-and insult-dependent manner and follow expression of p16 ink4a > SAHF formation is common in oncogene-induced senescence.
Load-bearingStrength:boosted· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“γH2AX and other functional markers of activated DDR can conveniently be assessed on tissue sections.13,48,[53][54][55]”
§ Senescence-associated heterochromatin foci are dispensable for cellular senescence, occur in a cell type-and insult-dependent manner and follow expression of p16 ink4a > Discussion
What the sources say
- Not checked yetcites [13]
- Not checked yetcites [48]
- Not checked yetcites [53]
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“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.”
§ Senescence-associated heterochromatin foci are dispensable for cellular senescence, occur in a cell type-and insult-dependent manner and follow expression of p16 ink4a > SAHF formation is common in oncogene-induced senescence.
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
In the paper
“a scenario that we recently reported to induce cellular senescence in the subpopulations of various human cell types, both normal and cancer-derived”
§ Senescence-associated heterochromatin foci are dispensable for cellular senescence, occur in a cell type-and insult-dependent manner and follow expression of p16 ink4a > SAHF formation is common in oncogene-induced senescence.
What the sources say
- Not checked yetcites [42]
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“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).”
§ Senescence-associated heterochromatin foci are dispensable for cellular senescence, occur in a cell type-and insult-dependent manner and follow expression of p16 ink4a > SAHF formation is common in oncogene-induced senescence.
Load-bearingStrength:hedged· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
In the paper
“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”
§ Senescence-associated heterochromatin foci are dispensable for cellular senescence, occur in a cell type-and insult-dependent manner and follow expression of p16 ink4a > SAHF formation is common in oncogene-induced senescence.
What the sources say
- Not checked yetcites [48]
Strength:plain· not yet calibratedCausal:correlational· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Several chemotherapeutic drugs including etoposide, 43 hydroxyurea 44 and doxorubicin 45,46 are known to induce premature senescence in human cells.”
§ Senescence-associated heterochromatin foci are dispensable for cellular senescence, occur in a cell type-and insult-dependent manner and follow expression of p16 ink4a > SAHF formation is common in oncogene-induced senescence.
What the sources say
- Not checked yetcites [43]
- Not checked yetcites [44]
- Not checked yetcites [45]
- Not checked yetcites [46]
Strength:boosted· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Whereas SAHF formation is shared by diverse cultured cell types under oncogenic stress, SAHF are cell-type-restricted under genotoxin-induced and replicative senescence.”
§ Senescence-associated heterochromatin foci are dispensable for cellular senescence, occur in a cell type-and insult-dependent manner and follow expression of p16 ink4a > Introduction
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“The diagnoses were independently verified by two experienced pathologists according to the established criteria of classification recommended by the World Health Organization.”
§ Senescence-associated heterochromatin foci are dispensable for cellular senescence, occur in a cell type-and insult-dependent manner and follow expression of p16 ink4a > Additional information
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Alpha-tubulin was used as a marker to ensure equal loading.”
§ Senescence-associated heterochromatin foci are dispensable for cellular senescence, occur in a cell type-and insult-dependent manner and follow expression of p16 ink4a > Additional information
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“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”
§ Senescence-associated heterochromatin foci are dispensable for cellular senescence, occur in a cell type-and insult-dependent manner and follow expression of p16 ink4a > Discussion
What the sources say
- Not checked yetcites [32]
Strength:hedged· not yet calibratedCausal:conditional· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“For quantitative and comparative imaging, identical image acquisition parameters were used.”
§ Senescence-associated heterochromatin foci are dispensable for cellular senescence, occur in a cell type-and insult-dependent manner and follow expression of p16 ink4a > Discussion
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesProbably not a substantial claim.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“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.”
§ Senescence-associated heterochromatin foci are dispensable for cellular senescence, occur in a cell type-and insult-dependent manner and follow expression of p16 ink4a > Additional information
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“The results shown are averages (with 95% confidence interval, tested by unpaired t-test) of a minimum of three independent experiments.”
§ Senescence-associated heterochromatin foci are dispensable for cellular senescence, occur in a cell type-and insult-dependent manner and follow expression of p16 ink4a > Data analysis and statistics.
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“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”
§ Senescence-associated heterochromatin foci are dispensable for cellular senescence, occur in a cell type-and insult-dependent manner and follow expression of p16 ink4a > Discussion
What the sources say
- Not checked yetcites [4]
- Not checked yetcites [62]
- Not checked yetcites [63]
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“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.”
§ Senescence-associated heterochromatin foci are dispensable for cellular senescence, occur in a cell type-and insult-dependent manner and follow expression of p16 ink4a > Discussion
Strength:hedged· not yet calibratedCausal:conditional· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
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”
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?
In the citing paper
“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]
In the citing paper
“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
MinorReference 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.
“the most recently described senescence mode induced by bacterial intoxication, 42”
“42. te Poele RH, Okorokov AL, Jardine L, Cummings J, Joel SP. DNA damage is able to induce senescence in tumor cells in vitro and in vivo. Cancer Res 2002; 62:1876-83.”
Error bars are described as both confidence intervals and standard deviations
MinorThe 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.
“The results shown are averages (with 95% confidence interval, tested by unpaired t-test) of a minimum of three independent experiments.”
“error bars represent the SD of three separate experiments.”
Holotoxin-preparation citations do not match the listed papers
MinorThe 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.
“Preparation of CdtA, CdtB and CdtC subunits and reconstitution of the active holotoxin (HdCDT) was previously described in references 47 and 75.”
“47. Bartkova J, Rezaei N, Liontos M, Karakaidos P, Kletsas D, Issaeva N, et al. Oncogene-induced senescence is part of the tumorigenesis barrier imposed by DNA damage checkpoints. Nature 2006; 444:633-7.”
Reference 48 does not match the cited earlier study
MinorThe 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.
“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”
“48. Seo HJ, Park HJ, Choi HS, Hwang SY, Park JS, Seong YS. BMI-1026 treatment can induce SAHF formation by activation of Erk1/2. BMB Rep 2008; 41:523-8.”
Citations
Cites
A biomarker that identifies senescent human cells in culture and in aging skin in vivo.
Dimri, G. P., Lee, X., Basile, G., Acosta, M., Scott, G., Roskelley, C., Medrano, E. E., Linskens, M., Rubelj, I., & Pereira-Smith, O. (1995) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.92.20.9363 · Cited by 7,477
The DNA-damage response in human biology and disease
Jackson, S. P., & Bartek, J. (2009) · Nature · doi:10.1038/nature08467 · Cited by 6,092
DNA double-stranded breaks induce histone H2AX phosphorylation on serine 139
Rogakou, E. P., Pilch, D. R., Orr, A. H., Ivanova, V. S., & Bonner, W. M. (1998) · Journal of Biological Chemistry · doi:10.1074/jbc.273.10.5858 · Cited by 5,438
Oncogenic ras provokes premature cell senescence associated with accumulation of p53 and p16INK4a
Serrano, M., Lin, A. W., McCurrach, M. E., Beach, D., & Lowe, S. W. (1997) · Cell · doi:10.1016/s0092-8674(00)81902-9 · Cited by 5,218 · cited 2×
“Another important aspect of our study is the close correlation of the ability to form SAHF and the increased level of p16, a CDK inhibitor whose involvement in cellular senescence and also SAHF formation has been widely studied.(4,22,32,40,56-60) Our present findings are consistent with the proposed causal role of p16…”
ResultCellular senescence: when bad things happen to good cells
Campisi, J., & d'Adda di Fagagna, F. (2007) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm2233 · Cited by 4,441
DNA damage response as a candidate anti-cancer barrier in early human tumorigenesis
Bartkova, J., Hořejší, Z., Koed, K., Krämer, A., Tort, F., Zieger, K., Guldberg, P., Sehested, M., Nesland, J. M., Lukas, C., et al. (2005) · Nature · doi:10.1038/nature03482 · Cited by 2,688
Self-citationOxidative stress shortens telomeres
von Zglinicki, T. (2002) · Trends in Biochemical Sciences · doi:10.1016/s0968-0004(02)02110-2 · Cited by 2,524
Senescent cells, tumor suppression, and organismal aging: good citizens, bad neighbors
Campisi, J. (2005) · Cell · doi:10.1016/j.cell.2005.02.003 · Cited by 2,379
Persistent DNA damage signalling triggers senescence-associated inflammatory cytokine secretion
Rodier, F., Coppé, J.-P., Patil, C. K., Hoeijmakers, W. A. M., Muñoz, D. P., Raza, S. R., Freund, A., Campeau, E., Davalos, A. R., & Campisi, J. (2009) · Nature Cell Biology · doi:10.1038/ncb1909 · Cited by 2,232
Activation of the DNA damage checkpoint and genomic instability in human precancerous lesions
Gorgoulis, V. G., Vassiliou, L.-V. F., Karakaidos, P., Zacharatos, P., Kotsinas, A., Liloglou, T., Venere, M., DiTullio, R. A., Kastrinakis, N. G., Levy, B., et al. (2005) · Nature · doi:10.1038/nature03485 · Cited by 2,009
Oncogene-induced senescence is part of the tumorigenesis barrier imposed by DNA damage checkpoints
Bartkova, J., Rezaei, N., Liontos, M., Karakaidos, P., Kletsas, D., Issaeva, N., Vassiliou, L.-V. F., Kolettas, E., Niforou, K., Zoumpourlis, V. C., et al. (2006) · Nature · doi:10.1038/nature05268 · Cited by 1,986
Self-citationChemokine signaling via the CXCR2 receptor reinforces senescence
Acosta, J. C., O'Loghlen, A., Banito, A., Guijarro, M. V., Augert, A., Raguz, S., Fumagalli, M., Da Costa, M., Brown, C., Popov, N., et al. (2008) · Cell · doi:10.1016/j.cell.2008.03.038 · Cited by 1,801
Reversal of human cellular senescence: roles of the p53 and p16 pathways
Beauséjour, C. M., Krtolica, A., Galimi, F., Narita, M., Lowe, S. W., Yaswen, P., & Campisi, J. (2003) · The EMBO Journal · doi:10.1093/emboj/cdg417 · Cited by 1,457
Herbig, U., Jobling, W. A., Chen, B. P. C., Chen, D. J., & Sedivy, J. M. (2004) · Molecular Cell · doi:10.1016/s1097-2765(04)00256-4 · Cited by 1,344
Oncogene-induced senescence as an initial barrier in lymphoma development
Braig, M., Lee, S., Loddenkemper, C., Rudolph, C., Peters, A. H. F. M., Schlegelberger, B., Stein, H., Dörken, B., Jenuwein, T., & Schmitt, C. A. (2005) · Nature · doi:10.1038/nature03841 · Cited by 1,220
A Senescence Program Controlled by p53 and p16INK4a Contributes to the Outcome of Cancer Therapy
Schmitt, C. A., Fridman, J. S., Yang, M., Lee, S., Baranov, E., Hoffman, R. M., & Lowe, S. W. (2002) · Cell · doi:10.1016/s0092-8674(02)00734-1 · Cited by 1,050
The Regulation of INK4/ARF in Cancer and Aging
Kim, W. Y., & Sharpless, N. E. (2006) · Cell · doi:10.1016/j.cell.2006.10.003 · Cited by 1,009
Production and purification of lentiviral vectors
Tiscórnia, G., Singer, O., & Verma, I. M. (2006) · Nature Protocols · doi:10.1038/nprot.2006.37 · Cited by 974
Wajapeyee, N., Serra, R. W., Zhu, X., Mahalingam, M., & Green, M. R. (2008) · Cell · doi:10.1016/j.cell.2007.12.032 · Cited by 903
Zhang, R., Poustovoitov, M. V., Ye, X., Santos, H. A., Chen, W., Daganzo, S. M., Erzberger, J. P., Serebriiskii, I. G., Canutescu, A. A., Dunbrack, R. L., et al. (2005) · Developmental Cell · doi:10.1016/j.devcel.2004.10.019 · Cited by 699
DNA damage response and cellular senescence in tissues of aging mice
Wang, C., Jurk, D., Maddick, M., Nelson, G., Martin‐Ruiz, C., & Von Zglinicki, T. (2009) · Aging Cell · doi:10.1111/j.1474-9726.2009.00481.x · Cited by 696
(2002) · PubMed · Cited by 640
A novel role for high-mobility group A proteins in cellular senescence and heterochromatin formation
Narita, M., Narita, M., Krizhanovsky, V., Nuñez, S., Chicas, A., Hearn, S. A., Myers, M. P., & Lowe, S. W. (2006) · Cell · doi:10.1016/j.cell.2006.05.052 · Cited by 629
Accumulation of senescent cells in Mitotic tissue of aging primates
Jeyapalan, J. C., Ferreira, M., Sedivy, J. M., & Herbig, U. (2007) · Mechanisms of Ageing and Development · doi:10.1016/j.mad.2006.11.008 · Cited by 571
p16 INK4A is a robust in vivo biomarker of cellular aging in human skin
Ressler, S., Bartkova, J., Niederegger, H., Bartek, J., Scharffetter‐Kochanek, K., Jansen‐Dürr, P., & Wlaschek, M. (2006) · Aging Cell · doi:10.1111/j.1474-9726.2006.00231.x · Cited by 557
(1999) · PubMed · Cited by 546
Putative telomere-independent mechanisms of replicative aging reflect inadequate growth conditions
Ramirez, R. D., Morales, C. P., Herbert, B.-S., Rohde, J. M., Passons, C., Shay, J. W., & Wright, W. E. (2001) · Genes & Development · doi:10.1101/gad.859201 · Cited by 444
Human cell senescence as a DNA damage response
Zglinicki, T. V., Saretzki, G., Ladhoff, J., Fagagna, F. D. D., & Jackson, S. P. (2005) · Mechanisms of Ageing and Development · doi:10.1016/j.mad.2004.09.034 · Cited by 419
Molecular dissection of formation of senescence-associated heterochromatin foci
Zhang, R., Chen, W., & Adams, P. D. (2007) · Molecular and Cellular Biology · doi:10.1128/mcb.02019-06 · Cited by 415
Growth stimulation leads to cellular senescence when the cell cycle is blocked
Demidenko, Z. N., & Blagosklonny, M. V. (2008) · Cell Cycle · doi:10.4161/cc.7.21.6919 · Cited by 396
Cellular senescence: putting the paradoxes in perspective
Campisi, J. (2011) · Current Opinion in Genetics & Development · doi:10.1016/j.gde.2010.10.005 · Cited by 368
Martin, J. A., & Buckwalter, J. A. (2003) · Journal of Bone and Joint Surgery · doi:10.2106/00004623-200300002-00014 · Cited by 320
PML Is a Direct p53 Target that Modulates p53 Effector Functions
de Stanchina, E., Querido, E., Narita, M., Davuluri, R. V., Pandolfi, P. P., Ferbeyre, G., & Lowe, S. W. (2004) · Molecular Cell · doi:10.1016/s1097-2765(04)00062-0 · Cited by 312
Coppé, J.-P., Patil, C. K., Rodier, F., Sun, Y., Muñoz, D. P., Goldstein, J., Nelson, P. S., Desprez, P.-Y., & Campisi, J. (2008) · PLoS Biology · doi:10.1371/journal.pbio.0060301 · Cited by 302
Cellular senescence and cancer treatment
Schmitt, C. A. (2007) · Biochimica et Biophysica Acta (BBA) - Reviews on Cancer · doi:10.1016/j.bbcan.2006.08.005 · Cited by 254
Quantitative assessment of markers for cell senescence
Lawless, C., Wang, C., Jurk, D., Merz, A., Zglinicki, T. V., & Passos, J. F. (2010) · Experimental Gerontology · doi:10.1016/j.exger.2010.01.018 · Cited by 240
Id1 regulation of cellular senescence through transcriptional repression of p16/Ink4a
Alani, R. M., Young, A. Z., & Shifflett, C. B. (2001) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.141235398 · Cited by 231
γ-H2AX in Cancer Cells: A Potential Biomarker for Cancer Diagnostics, Prediction and Recurrence
Martin, O. A., & Bonner, W. M. (2006) · Cell Cycle · doi:10.4161/cc.5.24.3569 · Cited by 194
p16Ink4a in Melanocyte Senescence and Differentiation
Sviderskaya, E. V. (2002) · JNCI Journal of the National Cancer Institute · doi:10.1093/jnci/94.6.446 · Cited by 181
Ye, X., Zerlanko, B. J., Zhang, R., Somaiah, N., Lipinski, M., Salomoni, P., & Adams, P. D. (2007) · Molecular and Cellular Biology · doi:10.1128/mcb.01592-06 · Cited by 177
Bártek, J., Lukas, J., & Bártková, J. (2007) · Cell Cycle · doi:10.4161/cc.6.19.4754 · Cited by 154
Self-citationFrisan, T., Cortes-Bratti, X., Chaves‐Olarte, E., Stenerlöw, B., & Thelestam, M. (2003) · Cellular Microbiology · doi:10.1046/j.1462-5822.2003.00311.x · Cited by 153
ATM Activation in Normal Human Tissues and Testicular Cancer
Bártková, J., Bakkenist, C. J., Meyts, E. R., Skakkebæk, N. E., Sehested, M., Lukas, J., Kastan, M. B., & Bártek, J. (2005) · Cell Cycle · doi:10.4161/cc.4.6.1742 · Cited by 144
Self-citationMartin-Ruiz, C. M., Saretzki, G. C., Petrie, J., Ladhoff, J., Jeyapalan, J. C., Wei, W., Sedivy, J. M., & von Zglinicki, T. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m311980200 · Cited by 134
Cytokine expression and signaling in drug-induced cellular senescence
Novakova, Z., Hubackova, S., Kosar, M., Janderova-Rossmeislova, L., Dobrovolna, J., Vasicova, P., Vancurova, M., Horejsi, Z., Hozak, P., Bartek, J., et al. (2010) · Oncogene · doi:10.1038/onc.2009.318 · Cited by 127
The DNA Damage Signaling Pathway Connects Oncogenic Stress to Cellular Senescence
Mallette, F. A., & Ferbeyre, G. (2007) · Cell Cycle · doi:10.4161/cc.6.15.4516 · Cited by 125
Bacterial intoxication evokes cellular senescence with persistent DNA damage and cytokine signalling
Blazkova, H., Krejčíková, K., Moudrý, P., Frisan, T., Hodný, Z., & Bártek, J. (2009) · Journal of Cellular and Molecular Medicine · doi:10.1111/j.1582-4934.2009.00862.x · Cited by 109
Irreversibility of cellular senescence: dual roles of p16INK4a/Rb-pathway in cell cycle control
Takahashi, A., Ohtani, N., & Hara, E. (2007) · Cell Division · doi:10.1186/1747-1028-2-10 · Cited by 101
Heterochromatin and its Relationship to Cell Senescence and Cancer Therapy
Zhang, R.-G., & Adams, P. (2007) · Cell Cycle · doi:10.4161/cc.6.7.4079 · Cited by 99
The Senescent Side of Tumor Suppression
Collado, M., & Serrano, M. (2005) · Cell Cycle · doi:10.4161/cc.4.12.2260 · Cited by 79
Mobilization and recruitment of HP1β: A bimodal response to DNA breakage
Ayoub, N., Jeyasekharan, A. D., & Venkitaraman, A. R. (2009) · Cell Cycle · doi:10.4161/cc.8.18.9486 · Cited by 76
Hubáčková, S., Nováková, Z., Krejčíková, K., Košař, M., Dobrovolná, J., Dušková, P., Hanzlíková, H., Vančurová, M., Baráth, P., Bártek, J., et al. (2010) · Cell Cycle · doi:10.4161/cc.9.15.12521 · Cited by 60
Aging-suppressants: Cellular senescence (hyperactivation) and its pharmacologic deceleration
Blagosklonny, M. V. (2009) · Cell Cycle · doi:10.4161/cc.8.12.8815 · Cited by 45
Pathways of oncogene-induced senescence in human melanocytic cells
Bansal, R., & Nikiforov, M. A. (2010) · Cell Cycle · doi:10.4161/cc.9.14.12251 · Cited by 45
Telomeres Limit Cancer Growth by Inducing Senescence: Long-Sought In Vivo Evidence Obtained
Sedivy, J. M. (2007) · Cancer Cell · doi:10.1016/j.ccr.2007.04.014 · Cited by 44
Rossmeislová, L., Nováková, Z., Dobrovolná, J., Philimonenko, V. V., Hozák, P., & Hodný, Z. (2007) · Journal of Structural Biology · doi:10.1016/j.jsb.2007.02.008 · Cited by 37
Induction of Transcriptionally Active Jun Proteins Regulates Drug-induced Senescence
Yogev, O., Anzi, S., Inoue, K., & Shaulian, E. (2006) · Journal of Biological Chemistry · doi:10.1074/jbc.m602865200 · Cited by 35
Mistrík, M., Oplustilova, L., Lukas, J., & Bártek, J. (2009) · Cell Cycle · doi:10.4161/cc.8.16.9331 · Cited by 23
Self-citationBártková, J., Moudrý, P., Hodný, Z., Lukáš, J., Meyts, E. R., & Bartek, J. J. (2010) · International Journal of Andrology · doi:10.1111/j.1365-2605.2010.01096.x · Cited by 21
Self-citationChromatin: a molecular interface between cancer and aging
Cruickshanks, H. A., & Adams, P. D. (2010) · Current Opinion in Genetics & Development · doi:10.1016/j.gde.2010.10.007 · Cited by 17
BMI-1026 treatment can induce SAHF formation by activation of Erk1/2
Seo, H.-J., Park, H. J., Choi, H.-S., Hwang, S.-Y., Park, J., & Seong, Y. (2008) · BMB Reports · doi:10.5483/bmbrep.2008.41.7.523 · Cited by 6
Flagged first, then by citations
Research works printed but not linked: 18
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- Bringold F, Serrano M. Tumor suppressors and onco- genes in cellular senescence. Exp Gerontol 2000; 35:317-29.
- Halazonetis TD, Gorgoulis VG, Bartek J. An onco- gene-induced DNA damage model for cancer develop- ment. Science 2008; 319:1352-5.
- Goodarzi AA, Noon AT, Jeggo PA. The impact of het- erochromatin on DSB repair. Biochem Soc Trans 2009; 37:569-76.
- 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.
- Adams PD. Remodeling of chromatin structure in senescent cells and its potential impact on tumor sup- pression and aging. Gene 2007; 397:84-93.
- 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.
- 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.
- 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.
- Collado M, Gil J, Efeyan A, Guerra C, Schuhmacher AJ, Barradas M, et al. Tumour biology: Senescence in premalignant tumours. Nature 2005; 436:642.
- Blagosklonny MV. Aging-suppressants: Cellular senes- cence (hyperactivation) and its pharmacologic decelera- tion. Cell Cycle 2009; 8:1883-7.
- 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.
- 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
Sorted by citations
Aging, Cellular Senescence, and Cancer
Campisi, J. (2013) · Annual Review of Physiology · doi:10.1146/annurev-physiol-030212-183653 · Cited by 2,954
Forging a signature of in vivo senescence
Sharpless, N. E., & Sherr, C. J. (2015) · Nature Reviews Cancer · doi:10.1038/nrc3960 · Cited by 1,104
Cellular senescence and tumor suppressor gene p16
Rayess, H., Wang, M. B., & Srivatsan, E. S. (2012) · International Journal of Cancer · doi:10.1002/ijc.27316 · Cited by 825
The DREAM complex: master coordinator of cell cycle-dependent gene expression
Sadasivam, S., & DeCaprio, J. A. (2013) · Nature Reviews Cancer · doi:10.1038/nrc3556 · Cited by 524
Markers of cellular senescence. Telomere shortening as a marker of cellular senescence
Bernadotte, A., Mikhelson, V. M., & Spivak, I. M. (2016) · Aging · doi:10.18632/aging.100871 · Cited by 466
Metadata
- 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
- 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
- bronze
- doi.org
- 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
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › 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
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.
A language model drew the claims from the paper on 2026-10-06, under version 3 of the claim definition (model deepseek-v4.1-flash, prompt extract-v3).
A second model labelled each claim on 2026-10-06 (model jev-1.13-20260917, definition revision gold-guideline-v0.2).
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 ›
Are you an author, or do you see a problem with this page? Request a review
