The DOI matches its Crossref record; 57 of the 86 references it cites were found in a registry or an index, and 29 are not checked yet; none of the 66 sources its claims cite is checked for support yet.
Shelterin: the protein complex that shapes and safeguards human telomeres
Open accessAbstract
Added by telomerase, arrays of TTAGGG repeats specify the ends of human chromosomes. A complex formed by six telomere-specific proteins associates with this sequence and protects chromosome ends. By analogy to other chromosomal protein complexes such as condensin and cohesin, I will refer to this complex as shelterin. Three shelterin subunits, TRF1, TRF2, and POT1 directly recognize TTAGGG repeats. They are interconnected by three additional shelterin proteins, TIN2, TPP1, and Rap1, forming a complex that allows cells to distinguish telomeres from sites of DNA damage. Without the protective activity of shelterin, telomeres are no longer hidden from the DNA damage surveillance and chromosome ends are inappropriately processed by DNA repair pathways. How does shelterin avert these events? The current data argue that shelterin is not a static structural component of the telomere. Instead, shelterin is emerging as a protein complex with DNA remodeling activity that acts together with several associated DNA repair factors to change the structure of the telomeric DNA, thereby protecting chromosome ends. Six shelterin subunits: TRF1, TRF2, TIN2, Rap1, TPP1, and POT1
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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
“Shelterin has exquisite specificity for telomeric TTAGGG repeats due to the presence of multiple TTAGGG recognition folds in the complex.”
§ Shelterin: the protein complex that shapes and safeguards human telomeres > Six shelterin subunits: TRF1, TRF2, TIN2, Rap1, TPP1, and POT1
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesNone of the sources cited for this claim have been checked yet.
In the paper
“All six shelterin subunits can be found in a single complex in fractionated nuclear extracts (Liu et al. 2004a;Ye et al. 2004a).”
§ Shelterin: the protein complex that shapes and safeguards human telomeres > Six shelterin subunits: TRF1, TRF2, TIN2, Rap1, TPP1, and POT1
What the sources say
- Not checked yetcites Liu et al. 2004a
- Not checked yetcites Ye et al. 2004a
Strength:plain· not yet calibratedCausal:correlational· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesThe paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“Three shelterin subunits, TRF1, TRF2, and POT1 directly recognize TTAGGG repeats.”
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesNone of the sources cited for this claim have been checked yet.
In the paper
“POT1 also has strong sequence specificity, binding single-stranded 5Ј-(T)TAGGGT TAG-3Ј sites both at a 3Ј end and at internal positions (Fig. 1; Lei et al. 2004;Loayza et al. 2004).”
§ Shelterin: the protein complex that shapes and safeguards human telomeres > Six shelterin subunits: TRF1, TRF2, TIN2, Rap1, TPP1, and POT1
What the sources say
- Not checked yetcites Lei et al. 2004
- Not checked yetcites Loayza et al. 2004
Load-bearingStrength:boosted· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIn the paper
“These deletions are dependent on two proteins implicated in HR, the Mre11 recombination repair complex and XRCC3, a Rad51 paralog associated with HJ resolution activity.”
§ Shelterin: the protein complex that shapes and safeguards human telomeres > Repression of HR
What the sources say
- Not checked yetcites Wang et al. 2004
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesNone of the sources cited for this claim have been checked yet.
In the paper
“This overhang has been proposed to invade the double-stranded telomeric DNA, base pairing with the C-strand and displacing the G-strand.”
- Also stated in: § Shelterin shapes telomeres · plain
“The strand invasion takes place at a distance from the physical end of the telomeres and therefore results in a large duplex lariat structure, the t-loop (Fig. 2).”
§ Shelterin: the protein complex that shapes and safeguards human telomeres > Shelterin shapes telomeres
What the sources say
- Not checked yetcites Griffith et al. 1999
- Not checked yetcites Stansel et al. 2001
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes- Also stated in: § Shelterin shapes telomeres · plain
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
“Recombination between telomeres and these elements could generate terminal deletions, extrachromosomal fragments, inversions, and translocations.”
§ Shelterin: the protein complex that shapes and safeguards human telomeres > Repression of HR
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIn the paper
“ALT cells, which contain abundant telomeric circles (Cesare and Griffith 2004”
§ Shelterin: the protein complex that shapes and safeguards human telomeres > Repression of HR
What the sources say
- Not checked yetcites Cesare and Griffith 2004
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesA 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
“Branch migration in the direction of the centromere could generate a double HJ”
§ Shelterin: the protein complex that shapes and safeguards human telomeres > Repression of HR
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesA 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
“On the other hand, these DNA-processing factors are potentially harmful to telomeres.”
§ Shelterin: the protein complex that shapes and safeguards human telomeres > Shelterin's affiliations with DNA repair factors
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes
- It may state two separate claims as one. 37
- The quote only partly states this claim. 2
- Probably not a substantial claim. 17
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
“A complex formed by six telomere-specific proteins associates with this sequence and protects chromosome ends.”
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
“They are interconnected by three additional shelterin proteins, TIN2, TPP1, and Rap1, forming a complex that allows cells to distinguish telomeres from sites of DNA damage.”
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
“The current data argue that shelterin is not a static structural component of the telomere.”
- Also stated in: § Shelterin: the protein complex that shapes and safeguards human telomeres · hedged
“Instead, shelterin is emerging as a protein complex with DNA remodeling activity that acts together with several associated DNA repair factors to change the structure of the telomeric DNA, thereby protecting chromosome ends.”
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
- Also stated in: § Shelterin: the protein complex that shapes and safeguards human telomeres · hedged
None of the sources cited for this claim have been checked yet.
In the paper
“The linchpin of shelterin is TIN2, which tethers TPP1/POT1 to TRF1 and TRF2.”
- Also stated in: § Six shelterin subunits: TRF1, TRF2, TIN2, Rap1, TPP1, and POT1 · plain
“TIN2 also connects TRF1 to TRF2 and this link contributes to the stabilization of TRF2 on telomeres (Liu et al. 2004a;Ye et al. 2004a).”
§ Shelterin: the protein complex that shapes and safeguards human telomeres > Six shelterin subunits: TRF1, TRF2, TIN2, Rap1, TPP1, and POT1
What the sources say
- Not checked yetcites Liu et al. 2004a
- Not checked yetcites Ye et al. 2004a
Strength:plain· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
- Also stated in: § Six shelterin subunits: TRF1, TRF2, TIN2, Rap1, TPP1, and POT1 · plain
None of the sources cited for this claim have been checked yet.
In the paper
“The SANT/ Myb-type DNA-binding domains of TRF1 and TRF2 each bind the sequence 5Ј-YTAGGGTTR-3Ј in duplex DNA, showing very low tolerance for single-base changes (Fig. 1; Bianchi et al. 1999;Court et al. 2005;Hanaoka et al. 2005).”
§ Shelterin: the protein complex that shapes and safeguards human telomeres > Six shelterin subunits: TRF1, TRF2, TIN2, Rap1, TPP1, and POT1
What the sources say
- Not checked yetcites Bianchi et al. 1999
- Not checked yetcites Court et al. 2005
- Not checked yetcites Hanaoka et al. 2005
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
“Without the protective activity of shelterin, telomeres are no longer hidden from the DNA damage surveillance and chromosome ends are inappropriately processed by DNA repair pathways.”
Tests✓ 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
“After inhibition of TRF2 or when telomeres become critically short, 53BP1, ␥-H2AX, the Mre11 complex, Rif1, and the phosphorylated form of ATM, ATM S1981-P, accumulate at chromosome ends.”
- Also stated in: § Shelterin inhibition activates the canonical DNA damage response · plain
“TIFs are also formed when other components of shelterin are inhibited (e.g., TIN2 or POT1) (Kim et al. 2004;Hockemeyer et al. 2005).”
§ Shelterin: the protein complex that shapes and safeguards human telomeres > Shelterin inhibition activates the canonical DNA damage response
What the sources say
- Not checked yetcites Takai et al. 2003
- Not checked yetcites Kim et al. 2004
- Not checked yetcites Hockemeyer et al. 2005
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
- Also stated in: § Shelterin inhibition activates the canonical DNA damage response · plain
In the paper
“Unexpectedly, it was found that the shelterin subunit TRF2 has a weak interaction with the ATM kinase (Karlseder et al. 2004), although ATM is not detectable at telomeres.”
- Also stated in: § An ATM inhibitor in shelterin? · plain
“In overexpression studies, TRF2 has the ability to inhibit S1981 phosphorylation and when TRF2 is abundant in the nucleoplasm, it has a dampening effect on the ATM signaling pathway (Karlseder et al. 2004).”
§ Shelterin: the protein complex that shapes and safeguards human telomeres > An ATM inhibitor in shelterin?
What the sources say
- Not checked yetcites Karlseder et al. 2004
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one. The quote only partly states this claim.
- Rests on an assumption: Shelterin is plentiful at chromosome ends and does not build up at other sites.
- Also stated in: § An ATM inhibitor in shelterin? · plain
In the paper
“The circular product of t-loop HR is also observed in ALT cells and at very low levels in unperturbed normal human cells.”
§ Shelterin: the protein complex that shapes and safeguards human telomeres > Repression of HR
What the sources say
- Not checked yetcites Wang et al. 2004
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
In the paper
“T-loop HR was discovered through a separation of function mutant of TRF2, TRF2 ⌬B , which protects telomeres from NHEJ but induces sudden telomere truncations.”
§ Shelterin: the protein complex that shapes and safeguards human telomeres > Repression of HR
What the sources say
- Not checked yetcites Wang et al. 2004
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
“resolution of this structure with crossover would delete the whole loop segment, leaving a drastically shortened telomere at the chromosome end.”
- Also stated in: § Repression of HR · plain
“Resolution of the double HJ in the direction shown will generate a shortened telomere and a circular telomeric DNA.”
§ Shelterin: the protein complex that shapes and safeguards human telomeres > Repression of HR
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
- Also stated in: § Repression of HR · plain
None of the sources cited for this claim have been checked yet.
In the paper
“This control of telomerase requires the ssDNA-binding activity of the shelterin component POT1 (Loayza and de Lange 2003;Liu et al. 2004b).”
- Also stated in: § Shelterin shapes telomeres · plain
“A POT1 mutant form that does not bind ssDNA results in complete loss of telomere length control.”
§ Shelterin: the protein complex that shapes and safeguards human telomeres > Shelterin shapes telomeres
What the sources say
- Not checked yetcites Loayza and de Lange 2003
- Not checked yetcites Liu et al. 2004b
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
- Also stated in: § Shelterin shapes telomeres · plain
None of the sources cited for this claim have been checked yet.
In the paper
“TRF2 can remodel an artificial telomeric substrate into loops (Griffith et al. 1999;Stansel et al. 2001).”
- Also stated in: § Shelterin shapes telomeres · hedged
“In vitro, TRF1 can loop, bend, and pair telomeric repeat arrays, activities that might stimulate the folding of telomeres in vivo, (Bianchi et al. 1997(Bianchi et al. , 1999;;Griffith et al. 1998) and TIN2 can enhance some of TRF1's architectural effects (Kim et al. 2003).”
§ Shelterin: the protein complex that shapes and safeguards human telomeres > Shelterin shapes telomeres
What the sources say
- Not checked yetcites Griffith et al. 1999
- Not checked yetcites Stansel et al. 2001
- Not checked yetcites Kim et al. 2003
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
- Also stated in: § Shelterin shapes telomeres · hedged
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
“On the one hand, the factors on its”
§ Shelterin: the protein complex that shapes and safeguards human telomeres > Shelterin's affiliations with DNA repair factors
Strength:hedged· not yet calibratedCausal:conditional· 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
“As T-SCE and t-loop HR are similar reactions (one taking place in cis, the other in trans)”
§ Shelterin: the protein complex that shapes and safeguards human telomeres > Repression of HR
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
“Shelterin is a key component of this pathway, representing the cis-acting inhibitor.”
- Also stated in: § Shelterin shapes telomeres · hedged
“Based on these data, the current model is that the amount of shelterin on a telomere determines the likelihood that its POT1 component can position itself on the 3Ј terminus and block telomerase (Fig. 2D).”
§ Shelterin: the protein complex that shapes and safeguards human telomeres > Shelterin shapes telomeres
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
- The authors state this as an assumption: Shelterin loading at a telomere is approximately proportional to the number of TTAGGG repeats.
- The authors state this as an assumption: Shelterin's inhibition of telomerase is stochastic and depends on how much shelterin is present at the telomere.
- The authors state this as an assumption: More shelterin on longer telomeres is assumed to raise the amount of POT1 loaded onto the overhang.
- The authors state this as an assumption: When POT1 occupies the 3' end, it is assumed to prevent telomerase from extending the telomere.
- Also stated in: § Shelterin shapes telomeres · hedged
In the paper
“Although the nuclease involved has not yet been identified, recent data shows that the nucleolytic processing of the 5Ј strand is controlled by shelterin.”
- Also stated in: § Shelterin shapes telomeres · plain
“When POT1 is inhibited, 5Ј ends lose their homogeneity and now end with AA, AT, TC, CC, CA, or AT (Hockemeyer et al. 2005).”
§ Shelterin: the protein complex that shapes and safeguards human telomeres > Shelterin shapes telomeres
What the sources say
- Not checked yetcites Hockemeyer et al. 2005
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
- Also stated in: § Shelterin shapes telomeres · plain
None of the sources cited for this claim have been checked yet.
In the paper
“POT1-like proteins are present in nearly all eukaryotes (de Lange 2001), a TRF1/2 like protein is found in fission yeast and in trypanosomes (Cooper et al. 1998;Sfeir et al. 2005), and Rap1 is present in fungi (Shore 1994;Chikashige and Hiraoka 2001;Kanoh and Ishikawa 2001).”
- Also stated in: § Six shelterin subunits: TRF1, TRF2, TIN2, Rap1, TPP1, and POT1 · hedged
“In contrast, the shelterin subunits TIN2 and TPP1 have so far only been found in vertebrates; their emergence may have coincided with the gain of a second TRF-like gene.”
§ Shelterin: the protein complex that shapes and safeguards human telomeres > Six shelterin subunits: TRF1, TRF2, TIN2, Rap1, TPP1, and POT1
What the sources say
- Not checked yetcites de Lange 2001
- Not checked yetcites Cooper et al. 1998
- Not checked yetcites Sfeir et al. 2005
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
- Also stated in: § Six shelterin subunits: TRF1, TRF2, TIN2, Rap1, TPP1, and POT1 · hedged
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
“Since these three shelterin subunits are connected through protein-protein interactions, shelterin has the capacity to recognize telomeric DNA with at least five DNA-binding domains (two each in TRF1 and TRF2 and one in POT1).”
- Also stated in: § Six shelterin subunits: TRF1, TRF2, TIN2, Rap1, TPP1, and POT1 · plain
“As a consequence, shelterin is uniquely qualified to distinguish telomeres from all other DNA ends.”
§ Shelterin: the protein complex that shapes and safeguards human telomeres > Six shelterin subunits: TRF1, TRF2, TIN2, Rap1, TPP1, and POT1
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one. The quote only partly states this claim.
- Also stated in: § Six shelterin subunits: TRF1, TRF2, TIN2, Rap1, TPP1, and POT1 · plain
None of the sources cited for this claim have been checked yet.
In the paper
“Nonhomologous end-joining (NHEJ) of two telomeres creates a circular or a dicentric chromosome.”
- Also stated in: § Preventing NHEJ and overhang processing · plain
“They occur when telomeres have become too short and when TRF2 is inhibited (for review, see de Lange 2002).”
- Also stated in: § Preventing NHEJ and overhang processing · plain
“Cells lacking DNA ligase IV or Ku70 have a 10-to 50-fold reduced ability to fuse telomeres after shelterin inhibition.”
§ Shelterin: the protein complex that shapes and safeguards human telomeres > Avoiding inappropriate repair
What the sources say
- Not checked yetcites de Lange 2002
- Not checked yetcites Smogorzewska et al. 2002
- Not checked yetcites Celli and de Lange 2005
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
- Also stated in: § Preventing NHEJ and overhang processing · plain
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
“These elements, referred to as Telomeric DNA-containing Double Minute chromosomes (TDMs) could be formed by recombination between a telomere and interstitial telomeric DNA on the same chromosome.”
§ Shelterin: the protein complex that shapes and safeguards human telomeres > Repression of HR
Strength:hedged· not yet calibratedCausal:conditional· 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
“T-loops are at risk for resolution by Holliday junction (HJ) resolvases because an HJ could be formed if the 5Ј end of the telomere base pairs with the displacement loop (D loop).”
§ Shelterin: the protein complex that shapes and safeguards human telomeres > Repression of HR
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
“If overhang protection is not sufficient to prevent the telomere damage response, shelterin must have at least one other mechanism to prevent detection of telomeres by the DNA damage surveillance.”
§ Shelterin: the protein complex that shapes and safeguards human telomeres > How does shelterin prevent a telomere damage signal?
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✗ Based: failsProbably not a substantial claim. The paper may give no reason why it holds. It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“In normal mouse and human cells, T-SCE is not frequent, but ALT cells, which maintain their telomeres by a recombination pathway, have very frequent T-SCE (Bailey et al. 2004;Bechter et al. 2004;Londono-Vallejo et al. 2004).”
- Also stated in: § Repression of HR · hedged
“The difference may be that T-SCEs are normally repressed and that ALT cells have loosened their control of HR at telomeres, allowing them to maintain their telomeres and therefore to survive (for review, see Neumann and Reddel 2002).”
§ Shelterin: the protein complex that shapes and safeguards human telomeres > Repression of HR
What the sources say
- Not checked yetcites Bailey et al. 2004
- Not checked yetcites Bechter et al. 2004
- Not checked yetcites Londono-Vallejo et al. 2004
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
- Also stated in: § Repression of HR · hedged
None of the sources cited for this claim have been checked yet.
In the paper
“that dysfunctional human telomeres indeed activate the DNA damage response pathway first emerged from experiments in which the shelterin subunit TRF2 was inhibited with a dominant-negative allele (TRF2 ⌬B⌬M ), that heterodimerizes with the endogenous TRF2, blocking its binding to DNA (van Steensel et al. 1998; for review, see de Lange 2002).”
- Also stated in: § Shelterin inhibition activates the canonical DNA damage response · plain
“The loss of TRF2 activates the ATM kinase pathway, leading to p53 up-regulation and a p21-mediated G1/S arrest (Karlseder et al. 1999).”
§ Shelterin: the protein complex that shapes and safeguards human telomeres > Shelterin inhibition activates the canonical DNA damage response
What the sources say
- Not checked yetcites van Steensel et al. 1998
- Not checked yetcites Karlseder et al. 1999
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
- Also stated in: § Shelterin inhibition activates the canonical DNA damage response · plain
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
“Due to the diminished amount of shelterin, the chance that POT1 loads on the overhang is reduced, leading to a higher chance that telomerase can elongate the telomere.”
§ Shelterin: the protein complex that shapes and safeguards human telomeres > Conclusions
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“NHEJ can also occur prior to DNA replication, giving rise to chromosome-type fusions in metaphase (not shown).”
§ Shelterin: the protein complex that shapes and safeguards human telomeres > Conclusions
Strength:plain· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✗ Based: failsProbably not a substantial claim. The paper’s conclusions may not depend on it. The paper may give no reason why it holds.
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
“Forced increase of POT1 on telomeres (through shelterin overexpression) increases the chance that telomerase will be blocked, resulting in telomere shortening.”
§ Shelterin: the protein complex that shapes and safeguards human telomeres > Conclusions
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes? Based: unclearIt may state two separate claims as one.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“The size of the loop is variable.”
§ Shelterin: the protein complex that shapes and safeguards human telomeres > Conclusions
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✗ Based: failsProbably not a substantial claim. The paper’s conclusions may not depend on it. The paper may give no reason why it holds.
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
“The presence of more shelterin on longer telomeres is proposed to increase the loading of POT1 on the telomeric overhang.”
§ Shelterin: the protein complex that shapes and safeguards human telomeres > Conclusions
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✗ Based: failsProbably not a substantial claim. The paper may give no reason why it holds.
- The authors state this as an assumption: The t-loop is unlikely to be a substrate for telomerase.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“Telomeres lose protection after inhibition of shelterin subunits (e.g., TRF2, TIN2, or POT1) or telomere attrition.”
§ Shelterin: the protein complex that shapes and safeguards human telomeres > Conclusions
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
“POT1 bound to the 3Ј end is proposed to block telomerase from acting.”
§ Shelterin: the protein complex that shapes and safeguards human telomeres > Conclusions
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✗ Based: failsProbably not a substantial claim. The paper may give no reason why it holds.
In the paper
“In mouse cells, p16 is induced, but its induction does not affect entry into S phase(Smogorzewska and de Lange 2002).”
§ Shelterin: the protein complex that shapes and safeguards human telomeres > Conclusions
What the sources say
- Not checked yetcites Smogorzewska and de Lange 2002
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“After replication, chromosome ends require processing in order to acquire a long 3Ј overhang.”
§ Shelterin: the protein complex that shapes and safeguards human telomeres > Conclusions
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✗ Based: failsProbably not a substantial claim. The paper may give no reason why it holds.
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
“which copies the G-rich telomeric strand and is therefore expected to be inhibited by G-quadruplexes”
§ Shelterin: the protein complex that shapes and safeguards human telomeres > Shelterin's affiliations with DNA repair factors
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
In the paper
“Another of shelterin's fair-weather friends is WRN, a RecQ helicase with 3Ј exonuclease activity.”
§ Shelterin: the protein complex that shapes and safeguards human telomeres > Shelterin's affiliations with DNA repair factors
What the sources say
- Not checked yetcites Opresko et al. 2002
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.
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
“At the same time, shelterin must control how these DNA repair factors act because some have the ability to destroy chromosome ends.”
§ Shelterin: the protein complex that shapes and safeguards human telomeres > Conclusions
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“the resulting terminal structure is a preferred binding site for POT1 in vitro.”
§ Shelterin: the protein complex that shapes and safeguards human telomeres > Conclusions
Strength:plain· not yet calibratedCausal:correlational· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✗ Based: failsProbably not a substantial claim. The paper’s conclusions may not depend on it. The paper may give no reason why it holds.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“Mre11/Rad50/Nbs1 | recombinational repair | t-loop formation/resolution? | associated with shelterin”
§ Shelterin: the protein complex that shapes and safeguards human telomeres > Conclusions
Strength:plain· not yet calibratedCausal:correlational· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✗ Based: failsProbably not a substantial claim. The paper’s conclusions may not depend on it. The paper may give no reason why it holds.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“required for t-loop HR”
§ Shelterin: the protein complex that shapes and safeguards human telomeres > Conclusions
Strength:plain· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✗ Based: failsProbably not a substantial claim. The paper’s conclusions may not depend on it. The paper may give no reason why it holds.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“Telomere damage activates the ATM kinase, which leads to a p53-dependent G1/S arrest and can induce either apoptosis or senescence.”
§ Shelterin: the protein complex that shapes and safeguards human telomeres > Conclusions
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
“Yet other aspects of shelterin, so far largely unknown, allow telomeres to evade detection by the DNA damage surveillance.”
§ Shelterin: the protein complex that shapes and safeguards human telomeres > Conclusions
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✗ Based: failsProbably not a substantial claim. The paper may give no reason why it holds.
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
“Inhibition of shelterin, or a mutant of POT1 that does not bind ssDNA, reduces the chance that telomerase will be blocked, resulting in telomere elongation.”
§ Shelterin: the protein complex that shapes and safeguards human telomeres > Conclusions
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“The resulting 5Ј end always has the sequence ATC-5Ј.”
§ Shelterin: the protein complex that shapes and safeguards human telomeres > Conclusions
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✗ Based: failsProbably not a substantial claim. The paper may give no reason why it holds.
None of the sources cited for this claim have been checked yet.
In the paper
“In vitro, WRN can resolve the t-loop structure and degrade the 3Ј overhang”
§ Shelterin: the protein complex that shapes and safeguards human telomeres > Shelterin's affiliations with DNA repair factors
What the sources say
- Not checked yetcites Opresko et al. 2002
- Not checked yetcites Opresko et al. 2004
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“The general function of WRN is to allow branch migration of HJs.”
§ Shelterin: the protein complex that shapes and safeguards human telomeres > Shelterin's affiliations with DNA repair factors
Strength:plain· 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
“Upon loss of shelterin, t-loops are proposed to be destabilized (or not formed), allowing engagement of the NHEJ pathway.”
§ Shelterin: the protein complex that shapes and safeguards human telomeres > Conclusions
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes? Based: unclearIt 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
“presumably so that the chromosome end is concealed from the NHEJ machinery.”
§ Shelterin: the protein complex that shapes and safeguards human telomeres > Conclusions
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✗ Based: failsProbably not a substantial claim. The paper may give no reason why it holds.
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
“This activity was recently proposed to be necessary for telomere replication”
§ Shelterin: the protein complex that shapes and safeguards human telomeres > Shelterin's affiliations with DNA repair factors
Strength:hedged· not yet calibratedCausal:conditional· 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
“WRN interacts with TRF2 and can be detected at telomeres by ChIP and IF in S phase (Opresko et al. 2002”
§ Shelterin: the protein complex that shapes and safeguards human telomeres > Shelterin's affiliations with DNA repair factors
What the sources say
- Not checked yetcites Opresko et al. 2002
- Not checked yetcites Crabbe et al. 2004
- Not checked yetcites Machwe et al. 2004
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
In the paper
“Telomere dysfunction also induces p16(Jacobs and de Lange 2004), which can contribute to the inhibition of proliferation in p53-deficient human cells.”
§ Shelterin: the protein complex that shapes and safeguards human telomeres > Conclusions
What the sources say
- Not checked yetcites Jacobs and de Lange 2004
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
“Shelterin recognizes telomeric DNA and remodels it into a t-loop”
§ Shelterin: the protein complex that shapes and safeguards human telomeres > Conclusions
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes? Based: unclearIt may state two separate claims as one.
The authors state this as an assumption.
Shelterin loading at a telomere is approximately proportional to the number of TTAGGG repeats.
“Since the amount of shelterin bound to a telomere is roughly proportional to the length of the TTAGGG repeat array, longer telomeres are proposed to have a greater probability of inhibiting telomerase.”
The authors state this as an assumption.
Shelterin's inhibition of telomerase is stochastic and depends on how much shelterin is present at the telomere.
“In the model, telomerase inhibition is a stochastic process influenced by the total amount of shelterin on a telomere.”
The authors state this as an assumption.
Telomerase probably cannot act on a t-loop.
“As the t-loop is unlikely to be a substrate for telomerase, telomeres are only shown in the”
The authors state this as an assumption.
More shelterin on longer telomeres is assumed to raise the amount of POT1 loaded onto the overhang.
“The presence of more shelterin on longer telomeres is proposed to increase the loading of POT1 on the telomeric overhang.”
The authors state this as an assumption.
When POT1 occupies the 3' end, it is assumed to prevent telomerase from extending the telomere.
“POT1 bound to the 3Ј end is proposed to block telomerase from acting.”
The paper relies on this without support.
Shelterin is plentiful at chromosome ends and does not build up at other sites.
“Shelterin is abundant at chromosome ends but does not accumulate elsewhere; it is present at telomeres throughout the cell cycle, and its known function is limited to telomeres.”
The authors state this as an assumption.
The t-loop is unlikely to be a substrate for telomerase.
“As the t-loop is unlikely to be a substrate for telomerase”
The paper relies on this without support.
Interstitial telomeric DNA is not frequent in human cells but is abundant throughout chromosomes in many other vertebrates.
“Chromosome internal telomeric DNA is not frequent in human cells, but in many other vertebrates, such sequences are abundant throughout the chromosomes.”
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
“It is believed that the “Shelterin” complex stabilizes a lariat-like structure, named the telomere-loop (or t-loop for short) with the purpose of shielding the exposed end of linear chromosomes (de Lange, 2005).”
From Telomeres and cell senescence—size matters not (2017) · cites this paper as de Lange, 2005
In the citing paper
“With each cell division telomeres shorten progressively, due to the so called “endreplication problem”.”
From Stress, cell senescence and organismal ageing (2018) · cites this paper as de Lange, 2005
In the citing paper
“Telomeres are repetitive DNA sequences, bound by the six-subunit shelterin complex [86] that facilitates the formation of telomere loops (t-loop) to hide the telomere end [87,88], thus protecting the natural chromosome ends from signaling pathways that sense and act at DNA breaks.”
From Mechanisms and Regulation of Cellular Senescence (2021) · cites this paper as [86]
In the citing paper
“Critically shortened telomeres are frequently observed in early neoplastic lesions [86,346,347]”
From Mechanisms and Regulation of Cellular Senescence (2021) · cites this paper as [86]
In the citing paper
“TRF1 and TRF2 each interact with a common factor TRF1interacting nuclear factor (TIN2) (8), which nucleates a six-member complex, termed shelterin, that also includes telomeric repeat binding factor 2-interacting protein, protection of telomeres 1 (POT1) and TPP1 (9).”
From Telomeres and telomerase in cancer (2010) · cites this paper as [9]
In the citing paper
“Mammalian telomeres associate with the shelterin complex of six core proteins — telomeric-repeat binding factor 1 (TRF1), TRF2, TRF1 interacting protein 2 (TIN2), protection of telomeres 1 (POT1), the POT1 and TIN2 interacting protein TPP1 and the transcriptional repressor/activator protein RAP115, 16”
From Telomere dysfunction and tumour suppression: the senescence connection (2008) · cites this paper as [15]
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 stated article count differs from the numbered reference list
MinorThe additional-information text states that the article cites 84 articles, but the reference list is numbered through 85.
“This article cites 84 articles, 36 of which can be accessed free at:”
“85. Zhu, X.D., Niedernhofer, L., Kuster, B., Mann, M., Hoeijmakers, J.H., and de Lange, T. 2003. ERCC1/XPF removes the 3Ј over- hang from uncapped telomeres and represses formation of telomeric DNA-containing double minute chromosomes. Mol. Cell 12: 1489-1498.”
The cis/trans labels appear reversed for the two recombination reactions
MinorThe comparison assigns the cis reaction to T-SCE and the trans reaction to t-loop HR, in that order. Elsewhere, T-SCE is described as exchange between sister telomeres, whereas t-loop HR occurs within a telomere's own loop.
“As T-SCE and t-loop HR are similar reactions (one taking place in cis, the other in trans), their prevalence in ALT cells may be due to loss of a repressor that controls both.”
“The first is homologous recombination between sister telomeres, referred to as Telomere Sister Chromatid Exchange (T-SCE).”
Citations
Cites
DNA damage activates ATM through intermolecular autophosphorylation and dimer dissociation
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A DNA damage checkpoint response in telomere-initiated senescence
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“The view that deprotected telomeres activate the DNA damage response has been solidified by experiments in which DNA damage response factors were observed at telomeres (d’Adda di Fagagna et al. 2003; Takai et al. 2003).”
Mammalian Telomeres End in a Large Duplex Loop
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TRF2 Protects Human Telomeres from End-to-End Fusions
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“For instance, p53-deficient mice better tolerate the consequences of telomere shortening in the later generations of telomerase-deficient mice (Chin et al. 1999).”
Flagged first, then by citations
Research works printed but not linked: 2
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- 1992, Mol. Cell. Biol., 12, 4834
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Metadata
- Authors
- de Lange, T.
- Venue
- Genes & Development
- Publisher
- Cold Spring Harbor Laboratory
- Published
- 2005-09-15
- Volume
- 19
- Issue
- 18
- Pages
- 2100-2110
- ISSN
- 0890-9369 (ISSN-L)
- 1549-5477
- OpenAlex
- W2160185049
- Cited by
- 3,056
- References
- 86
- Citations by year
- 2026: 74 · 2025: 97 · 2024: 114 · 2023: 140 · 2022: 106 · 2021: 196 · 2020: 140 · 2019: 150 · 2018: 138 · 2017: 182 · 2016: 175 · 2015: 164 · 2014: 162 · 2013: 164 · 2012: 156
- Type
- posted content
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Genes & Development (publishedVersion)
- PubMed (publishedVersion)
- HighWire Press Open Archive (submittedVersion)
- Funders
- National Institutes of Health (1f31gm016642-01, CA76027, GM49046)
- National Cancer Institute (CA76027-8, R01CA076027)
- National Institute of General Medical Sciences (GM49046-12, GM16642-7)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Telomeres, Telomerase, and Senescence
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA Repair Mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA and Nucleic Acid Chemistry
- Keywords
- shelterin, telomeres, telomere protection, TRF1, TRF2, POT1, TIN2, TPP1, Rap1, TTAGGG repeats, telomerase, DNA repair, chromosome end protection
- MeSH terms
- Shelterin Complex, Antigens, Surface, Binding Sites, DNA Damage, Humans, Membrane Glycoproteins, Models, Biological, Peptide Hydrolases, Protein Binding, Proteins, Cell Adhesion Molecules, Telomere, Protein Structure, Tertiary, Tandem Repeat Sequences, rap1 GTP-Binding Proteins, Protein Subunits, Telomere-Binding Proteins, Telomeric Repeat Binding Protein 1, Telomeric Repeat Binding Protein 2, Chromosomal Instability, Multiprotein Complexes
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