Evidence map›Paper›PMID 33673424›Full record

ArticleInternational journal of molecular sciences2021

A Role for Human DNA Polymerase λ in Alternative Lengthening of Telomeres.

Elisa Mentegari, Federica Bertoletti, Miroslava Kissova, Elisa Zucca, Silvia Galli, Giulia Tagliavini, Anna Garbelli, Antonio Maffia, Silvia Bione, Elena Ferrari and 10 more

Open access · goldAbstract read
In one paragraph

Article in International journal of molecular sciences, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
0.4field-weighted citation impact, top 43% of its field
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

3 citing papers in PubMed, 3 citations in OpenAlex.

  1. Article
  2. Article
  3. Review
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

20 authors at 6 institutions in 3 countries.

Elisa MentegariInstitute of Molecular Genetics IGM-CNR "Luigi Luca Cavalli-Sforza", Via Abbiategrasso 207, I-27100 Pavia, Italy.
Federica BertolettiInstitute of Molecular Genetics IGM-CNR "Luigi Luca Cavalli-Sforza", Via Abbiategrasso 207, I-27100 Pavia, Italy.
Miroslava KissovaInstitute of Molecular Genetics IGM-CNR "Luigi Luca Cavalli-Sforza", Via Abbiategrasso 207, I-27100 Pavia, Italy.ORCID 0000-0001-9798-9131
Elisa ZuccaInstitute of Molecular Genetics IGM-CNR "Luigi Luca Cavalli-Sforza", Via Abbiategrasso 207, I-27100 Pavia, Italy.
Silvia GalliInstitute of Molecular Genetics IGM-CNR "Luigi Luca Cavalli-Sforza", Via Abbiategrasso 207, I-27100 Pavia, Italy.
Giulia TagliaviniInstitute of Molecular Genetics IGM-CNR "Luigi Luca Cavalli-Sforza", Via Abbiategrasso 207, I-27100 Pavia, Italy.
Anna GarbelliInstitute of Molecular Genetics IGM-CNR "Luigi Luca Cavalli-Sforza", Via Abbiategrasso 207, I-27100 Pavia, Italy.
Antonio MaffiaInstitute of Molecular Genetics IGM-CNR "Luigi Luca Cavalli-Sforza", Via Abbiategrasso 207, I-27100 Pavia, Italy.
Silvia BioneInstitute of Molecular Genetics IGM-CNR "Luigi Luca Cavalli-Sforza", Via Abbiategrasso 207, I-27100 Pavia, Italy.
Elena FerrariDepartment of Molecular Mechanisms of Disease, University of Zürich-Irchel, Winterthurerstrasse 190, CH-8057 Zürich, Switzerland.
Fabrizio d'Adda di FagagnaInstitute of Molecular Genetics IGM-CNR "Luigi Luca Cavalli-Sforza", Via Abbiategrasso 207, I-27100 Pavia, Italy.ORCID 0000-0002-9603-5966
Sofia FranciaInstitute of Molecular Genetics IGM-CNR "Luigi Luca Cavalli-Sforza", Via Abbiategrasso 207, I-27100 Pavia, Italy.
Simone SabbionedaInstitute of Molecular Genetics IGM-CNR "Luigi Luca Cavalli-Sforza", Via Abbiategrasso 207, I-27100 Pavia, Italy.
Liuh-Yow ChenSwiss Institute for Experimental Cancer Research (ISREC), School of Life Sciences, Frontiers in Genetics National Center of Competence in Research, Ecole Polytechnique Fédérale de Lausanne (EPFL), Station 19, CH-1015 Lausanne, Switzerland.ORCID 0000-0002-9857-068X
Joachim LingnerSwiss Institute for Experimental Cancer Research (ISREC), School of Life Sciences, Frontiers in Genetics National Center of Competence in Research, Ecole Polytechnique Fédérale de Lausanne (EPFL), Station 19, CH-1015 Lausanne, Switzerland.
Valerie BergoglioUMR1037 INSERM, Cancer Research Center of Toulouse, 2 Avenue Curien, 31037 Toulouse, France.ORCID 0000-0003-2773-3178
Jean-Sébastien HoffmannLaboratoire d'Excellence Toulouse Cancer (TOUCAN), Laboratoire de Pathologie, Institut Universitaire du Cancer-Toulouse, Oncopole, 1 avenue Irène-Joliot-Curie, 31059 Toulouse, France.ORCID 0000-0003-2222-354X
Ulrich HübscherDepartment of Molecular Mechanisms of Disease, University of Zürich-Irchel, Winterthurerstrasse 190, CH-8057 Zürich, Switzerland.
Emmanuele CrespanInstitute of Molecular Genetics IGM-CNR "Luigi Luca Cavalli-Sforza", Via Abbiategrasso 207, I-27100 Pavia, Italy.
Giovanni MagaInstitute of Molecular Genetics IGM-CNR "Luigi Luca Cavalli-Sforza", Via Abbiategrasso 207, I-27100 Pavia, Italy.ORCID 0000-0001-8092-1552
Istituto di Genetica Molecolare · ITÉcole Polytechnique Fédérale de Lausanne · CHUniversity of Zurich · CHIFOM · ITInserm · FRInstitut universitaire du cancer de Toulouse Oncopole · FR

Funding

Associazione Italiana per la Ricerca sul Cancro IG20762Associazione Italiana per la Ricerca sul Cancro MFAG2016 18811Associazione Italiana per la Ricerca sul Cancro Start-up Grant 12710Fondazione Italiana per la Ricerca sul Cancro 24263
6 · The paper itself

Abstract

Telomerase negative cancer cell types use the Alternative Lengthening of Telomeres (ALT) pathway to elongate telomeres ends. Here, we show that silencing human DNA polymerase (Pol λ) in ALT cells represses ALT activity and induces telomeric stress. In addition, replication stress in the absence of Pol λ, strongly affects the survival of ALT cells. In vitro, Pol λ can promote annealing of even a single G-rich telomeric repeat to its complementary strand and use it to prime DNA synthesis. The noncoding telomeric repeat containing RNA TERRA and replication protein A negatively regulate this activity, while the Protection of Telomeres protein 1 (POT1)/TPP1 heterodimer stimulates Pol λ. Pol λ associates with telomeres and colocalizes with TPP1 in cells. In summary, our data suggest a role of Pol λ in the maintenance of telomeres by the ALT mechanism.

Indexed as

G-QuadruplexesTelomere HomeostasisAminopeptidasesCell Line, TumorDNA Polymerase betaHumansMultiprotein ComplexesReplication Protein ASerine ProteasesShelterin ComplexTelomereTelomere-Binding ProteinsACD protein, humanAminopeptidasesDNA Polymerase betaDNA polymerase beta2Multiprotein ComplexesPOT1 protein, humanReplication Protein ASerine ProteasesShelterin ComplexTelomere-Binding Proteinsalternative lengthening of telomeres (ALT), DNA polymerase λDNA double-strand breaks (DSBs), extra-chromosomal telomeric repeats (ECTRs), promyelocytic leukemia (PML) bodiesmicrohomology-mediated strand transfer (MMST) activitytelomere dysfunction-induced foci (TIFs), telomere stress

Identifiers

PMID33673424
PMCPMC7956399
OpenAlexW3134228340

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

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.