The DOI matches its Crossref record; 1 of the 1 references it cites were found in a registry or an index.
Separation of telomere protection from length regulation by two different point mutations at amino acid 492 of RTEL1
Open accessPreprint — published as 10.1093/nar/gkaf507 · Paper page
Abstract
RTEL1 is an essential DNA helicase that plays multiple roles in genome stability and telomere length regulation. A variant of RTEL1 with a lysine at position 492 is associated with short telomeres in Mus spretus , while a conserved methionine at this position is found in M. musculus , which has ultra-long telomeres. In humans, a missense mutation at this position ( Rtel1 M492I ) causes a fatal telomere biology disease termed Hoyeraal-Hreidarsson syndrome (HHS). Introducing the Rtel1 M492K mutation into M. musculus shortened the telomeres of the resulting strain, termed ‘Telomouse’, to the length of human telomeres. Here, we report on a mouse strain carrying the Rtel1 M492I mutation, termed ‘HHS mouse’. The HHS mouse telomeres are not as short as those of Telomice but nevertheless they display higher levels of telomeric DNA damage, fragility and recombination, associated with anaphase bridges and micronuclei. These observations indicate that the two mutations separate critical functions of RTEL1: M492K mainly reduces the telomere length setpoint, while M492I predominantly disrupts telomere protection. The two mouse models enable dissecting the mechanistic roles of RTEL1 and the different contributions of short telomeres and DNA damage to telomere biology diseases, genomic instability, cancer, and aging.
Overview
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
Verification
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.
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
Highly accurate protein structure prediction with AlphaFold
Jumper, J., Evans, R., Pritzel, A., Green, T., Figurnov, M., Ronneberger, O., Tunyasuvunakool, K., Bates, R., Žídek, A., Potapenko, A., et al. (2021) · Nature · doi:10.1038/s41586-021-03819-2 · Cited by 43,764
Flagged first, then by citations
Research works printed but not linked: 40
- 10.1146/annurev-genet-032918-021921 · DOI · Paper page
- Takai, H. , Aria, V. , Borges, P. , Yeeles, J.T.P. and de Lange, T. (2024) CST-polymerase alpha-primase solves a second telomere end-replication problem. Nature. · DOI
- Blackburn, E.H. and Collins, K. (2011) Telomerase: an RNP enzyme synthesizes DNA. Cold Spring Harb Perspect Biol, 3. · DOI
- 10.1182/blood.2021014299 · DOI
- 2024, Telomeres as hotspots for innate immunity and inflammation, DNA Repair (Amst), 133, 103591, 10.1016/j.dnarep.2023.103591 · DOI
- 2021, Telomeres and Cancer: Resolving the Paradox, Annu Rev Cancer Biol, 5, 59, 10.1146/annurev-cancerbio-050420-023410 · DOI
- 10.1016/j.cell.2004.05.026 · DOI · Paper page
- 10.1091/mbc.E12-03-0179 · DOI
- 10.1093/nar/gkaa503 · DOI
- 10.1038/s41467-023-42534-6 · DOI
- Cheng, K. and Wigley, D.B. (2018) DNA translocation mechanism of an XPD family helicase. Elife, 7. · DOI
- 10.1042/BST20170044 · DOI
- Hourvitz, N. , Awad, A. and Tzfati, Y. (2023) The many faces of the helicase RTEL1 at telomeres and beyond. Trends Cell Biol. · DOI
- 10.1126/science.1241779 · DOI
- 10.1016/j.cell.2009.06.021 · DOI · Paper page
- 10.1038/s41586-019-1744-8 · DOI
- 10.1016/j.molcel.2014.12.024 · DOI
- 10.1016/j.cell.2017.11.047 · DOI
- 10.1093/nar/gky173 · DOI
- 10.1093/nar/gku1402 · DOI
- 10.1038/s41467-021-23299-2 · DOI
- 10.1164/rccm.201408-1510OC · DOI
- 10.1182/bloodadvances.2017008110 · DOI
- 2023, Regulator of telomere elongation helicase 1 gene and its association with malignancy, Cancer Rep (Hoboken), 6, e1735, 10.1002/cnr2.1735 · DOI
- 10.1371/journal.pgen.1003695 · DOI
- 10.1007/s00439-013-1265-8 · DOI
- 10.1073/pnas.1300600110 · DOI
- 10.1093/hmg/ddt178 · DOI
- 10.1016/j.ajhg.2013.02.001 · DOI
- 10.1111/bjh.13442 · DOI
- 10.1371/journal.pone.0005666 · DOI
- 10.1038/nprot.2014.134 · DOI
- 10.1093/nar/gkt1315 · DOI
- 10.1038/nprot.2015.053 · DOI · Paper page
- 10.1073/pnas.92.11.4818 · DOI
- 10.4161/cc.7.22.7152 · DOI
- 10.1016/j.cell.2012.03.030 · DOI
- 10.1074/jbc.M112.374504 · DOI
- 10.1101/gad.330050.119 · DOI
- 10.1111/jeb.12568 · DOI
Metadata
- Authors
- Smoom, R., May, C. L., Lichtental, D., Skordalakes, E., Kaestner, K. H., & Tzfati, Y.
- Affiliations
- Hebrew University of Jerusalem (IL)
- University of Pennsylvania (US)
- Virginia Commonwealth University (US)
- Corresponding author
- Kaestner, Klaus H.
- Tzfati, Yehuda
- Venue
- Nucleic Acids Research
- Publisher
- openRxiv
- Published
- 2024-02-29
- Volume
- 53
- Issue
- 11
- ISSN
- 0305-1048 (ISSN-L)
- PMC
- PMC12203905
- OpenAlex
- W4411469096
- Cited by
- 4
- References
- 1
- Citations by year
- 2025: 3 · 2024: 1
- FWCI
- 1.92
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Nucleic Acids Research (publishedVersion, cc-by-nc)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion)
- PubMed Central (publishedVersion, cc-by-nc)
- PubMed (publishedVersion)
- PubMed Central (submittedVersion)
- Funders
- Hebrew University of Jerusalem
- Israel Science Foundation (2071/18, 1342/23, 2166/24)
- National Institutes of Health (5u01dk134995-04)
- National Heart, Lung, and Blood Institute (R01HL141852, R01HL127349)
- National Cancer Institute (R01CA249929, P30CA010815)
- National Institute of Diabetes and Digestive and Kidney Diseases (R37DK053839, R01-HL-127349, U01-DK-134995, R01-HL-141852, R01-CA249929, R01DK139049, P30DK050306)
- 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 › Nuclear Structure and Function
- Keywords
- RTEL1, telomere protection, telomere length regulation, Hoyeraal-Hreidarsson syndrome, DNA helicase, telomere biology disorders, telomeric DNA damage, telomere fragility, anaphase bridges, micronuclei, pulmonary fibrosis, genomic instability, mouse model
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
