The E3 ubiquitin ligase Rnf8 stabilizes Tpp1 to promote telomere end protection.
Open accessAbstract
The mammalian shelterin component TPP1 has essential roles in telomere maintenance and, together with POT1, is required for the repression of DNA damage signaling at telomeres. Here we show that in Mus musculus, the E3 ubiquitin ligase Rnf8 localizes to uncapped telomeres and promotes the accumulation of DNA damage proteins 53Bp1 and γ-H2ax. In the absence of Rnf8, Tpp1 is unstable, resulting in telomere shortening and chromosome fusions through the alternative nonhomologous end-joining (A-NHEJ) repair pathway. The Rnf8 RING-finger domain is essential for Tpp1 stability and retention at telomeres. Rnf8 physically interacts with Tpp1 to generate Ubc13-dependent Lys63 polyubiquitin chains that stabilize Tpp1 at telomeres. The conserved Tpp1 residue Lys233 is important for Rnf8-mediated Tpp1 ubiquitylation and localization to telomeres. Thus, Tpp1 is a newly identified substrate for Rnf8, indicating a previously unrecognized role for Rnf8 in telomere end protection.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
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?
Ubiquitination of human TPP1 signals the protein for proteasomal degradation, unlike murine TPP1 whose ubiquitination promotes telomere localization.
“Unlike murine TPP1, whose ubiquitination promotes telomere localization (Rai et al., 2011), the ubiquitination of human TPP1 signals the protein for proteasomal degradation.”
From USP7 Is a Master Regulator of Genome Stability (2020) · cites this paper as Rai et al., 2011
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
The citation lists haven’t been fetched yet
References 51 · Cited by 88
- Authors
- Rai, R., Li, J.-M., Zheng, H., Lok, G. T.-M., Deng, Y., Huen, M. S.-Y., Chen, J., Jin, J., & Chang, S.
- Affiliations
- Yale University (US)
- The University of Texas Health Science Center at Houston (US)
- The University of Texas MD Anderson Cancer Center (US)
- University of Hong Kong (HK)
- Corresponding author
- Chang, Sandy
- Venue
- Nature Structural & Molecular Biology
- Published
- 2011-11-20
- Volume
- 18
- Issue
- 12
- Pages
- 1400-1407
- ISSN
- 1545-9985 (ISSN-L)
- 1545-9993
- PMC
- PMC3657743
- OpenAlex
- W2027330624
- Cited by
- 88
- References
- 51
- Citations by year
- 2026: 2 · 2025: 1 · 2024: 3 · 2023: 4 · 2022: 16 · 2021: 3 · 2020: 5 · 2019: 6 · 2017: 4 · 2016: 11 · 2015: 6 · 2014: 10 · 2013: 9 · 2012: 8
- FWCI
- 5.89
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Structural & Molecular Biology (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- The HKU Scholars Hub (University of Hong Kong) (submittedVersion)
- Funders
- National Cancer Institute (R01CA092312, R01CA129037)
- Topics
- Health Sciences › Medicine › Physiology › Telomeres, Telomerase, and Senescence
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ubiquitin and proteasome pathways
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA Repair Mechanisms
- Keywords
- RNF8, E3 ubiquitin ligase, TPP1, shelterin, telomere protection, protein stability, Ubc13, RING domain, telomere shortening, chromosome fusion, DNA damage response, γH2AX, 53BP1, telomere capping
- MeSH terms
- Tumor Suppressor p53-Binding Protein 1, Animals, Chromosomal Proteins, Non-Histone, DNA Damage, DNA-Binding Proteins, Histones, Telomere, Protein Interaction Mapping, Chromosomes, Mammalian, Telomere-Binding Proteins, Ubiquitin-Protein Ligases, Mice, Ubiquitination, Protein Stability
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.
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
