Evidence map›Paper›PMID 40015989›Full record

ArticleGenes & development2025

Active telomere elongation by a subclass of cancer-associated POT1 mutations.

Annika Martin, Johannes Schabort, Rebecca Bartke-Croughan, Stella Tran, Atul Preetham, Robert Lu, Richard Ho, Jianpu Gao, Shirin Jenkins, John Boyle and 5 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Genes & development, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

6 citing papers in PubMed.

  1. How telomere attrition protects against cancer.Nature reviews. Genetics · 2026
    Review
  2. Decoding thebioRxiv : the preprint server for biology · 2026
    Article
  3. Article
  4. Article
  5. Article
  6. GermlineGenetics in medicine open · 2026
    Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

15 authors.

Annika Martin *Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, California 94720, USA.
Johannes Schabort *Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, California 94720, USA.
Rebecca Bartke-Croughan *Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, California 94720, USA.
Stella TranDepartment of Molecular and Cell Biology, University of California, Berkeley, Berkeley, California 94720, USA.
Atul PreethamDepartment of Molecular and Cell Biology, University of California, Berkeley, Berkeley, California 94720, USA.
Robert LuDepartment of Molecular and Cell Biology, University of California, Berkeley, Berkeley, California 94720, USA.
Richard HoDepartment of Molecular and Cell Biology, University of California, Berkeley, Berkeley, California 94720, USA.
Jianpu GaoDepartment of Molecular and Cell Biology, University of California, Berkeley, Berkeley, California 94720, USA.
Shirin JenkinsDepartment of Molecular and Cell Biology, University of California, Berkeley, Berkeley, California 94720, USA.
John BoyleDepartment of Molecular and Cell Biology, University of California, Berkeley, Berkeley, California 94720, USA.ORCID 0000-0001-6173-6765
George E GhanimMRC Laboratory of Molecular Biology; Cambridge CB2 0QH, United Kingdom.
Milind JagotaComputer Science Division, University of California, Berkeley, Berkeley, California 94720, USA.
Yun S SongComputer Science Division, University of California, Berkeley, Berkeley, California 94720, USA.ORCID 0000-0002-0734-9868
Hanqin LiDepartment of Molecular and Cell Biology, University of California, Berkeley, Berkeley, California 94720, USA; hockemeyer@berkeley.edu hanqinli@berkeley.edu.
Dirk HockemeyerDepartment of Molecular and Cell Biology, University of California, Berkeley, Berkeley, California 94720, USA; hockemeyer@berkeley.edu hanqinli@berkeley.edu.

Funding

Molecular Genetics of the Telomere Biology DisordersR01HL131744 · NHLBI · BAYLOR COLLEGE OF MEDICINE · PI BERTUCH, ALISON A, HOCKEMEYER, DIRK · 2016 to 2025
$4.5M
Robust and efficient statistical inference methods for genomicsR35GM134922 · NIGMS · UNIVERSITY OF CALIFORNIA BERKELEY · PI SONG, YUN S · 2020 to 2024
$2.0M
NHLBI NIH HHS R01 HL131744NIGMS NIH HHS R35 GM134922
6 · The paper itself

Abstract

Mutations in the shelterin protein POT1 are associated with diverse cancers and thought to drive carcinogenesis by impairing POT1's suppression of aberrant telomere elongation. To classify clinical variants of uncertain significance (VUSs) and identify cancer-driving loss-of-function mutations, we developed a locally haploid human stem cell system to evaluate >1900 POT1 mutations, including >600 VUSs. Unexpectedly, many validated familial cancer-associated POT1 (caPOT1) mutations are haplosufficient for cellular viability, indicating that some pathogenic alleles do not act through a loss-of-function mechanism. Instead, POT1's DNA damage response suppression and telomere length control are genetically separable. ATR inhibition enables isolation of frameshift mutants, demonstrating that the only essential function of POT1 is to repress ATR. Furthermore, comparison of caPOT1 and frameshift alleles reveals a class of caPOT1 mutations that elongate telomeres more rapidly than full loss-of-function alleles. This telomere length-promoting activity is independent from POT1's role in overhang sequestration and fill-in synthesis.

Indexed as

MutationNeoplasmsTelomereTelomere-Binding ProteinsTelomere HomeostasisAtaxia Telangiectasia Mutated ProteinsDNA DamageFrameshift MutationHumansShelterin ComplexAtaxia Telangiectasia Mutated ProteinsPOT1 protein, humanShelterin ComplexTelomere-Binding Proteinscancerdeep scanning mutagenesispluripotent stem cellsPOT1telomerasetelomere

Identifiers

PMID40015989
PMCPMC11960693

What OpenQuestion holds

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Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.