Evidence map›Paper›PMID 35588569›Full record

ReviewDNA repair2022

New twists to the ALTernative endings at telomeres.

Ragini Bhargava, Michelle Lee Lynskey, Roderick J O'Sullivan

Open access · greenAbstract readReview
In one paragraph

Review in DNA repair, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.

0numbers the graph read from it
0cells of the map it votes in
23citing papers in PubMed
3.9field-weighted citation impact, top 5% 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

23 citing papers in PubMed, 35 citations in OpenAlex.

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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

3 authors at 1 institution in 1 country.

Ragini BhargavaDepartment of Pharmacology and Chemical Biology, UPMC Hillman Cancer Center, University of Pittsburgh, Pittsburgh, PA, USA.
Michelle Lee LynskeyDepartment of Pharmacology and Chemical Biology, UPMC Hillman Cancer Center, University of Pittsburgh, Pittsburgh, PA, USA.
Roderick J O'SullivanDepartment of Pharmacology and Chemical Biology, UPMC Hillman Cancer Center, University of Pittsburgh, Pittsburgh, PA, USA. Electronic address: osullivanr@upmc.edu.
UPMC Hillman Cancer Center · US

Funding

VECTOR CORE FACILITYP30CA047904 · NCI · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI CHRISTOPHER J. BAKKENIST · 1988 to 2026
$158.0M
Inhibition of the ALT pathway by interfering with Poly-ADP-Ribose metabolismR01CA207209 · NCI · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI Roderick O'Sullivan · 2016 to 2026
$3.6M
The Prognostic Significance and Mechanistic Determination of Chromatin Remodeling Biomarkers in Non-Functional Pancreatic Neuroendocrine TumorR37CA263622 · NCI · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI Aatur Dilip Singhi · 2021 to 2026
$3.4M
Co-Regulation of Alternative Lengthening of Telomeres and Chromatin Dynamics in ATRX-DAXX deficient cancer cellsR01CA262316 · NCI · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI Roderick O'Sullivan · 2022 to 2026
$2.2M
NCI NIH HHS P30 CA047904NCI NIH HHS R01 CA207209NCI NIH HHS R01 CA262316NCI NIH HHS R37 CA263622
6 · The paper itself

Abstract

Activation of a telomere maintenance mechanism is key to achieving replicative immortality. Alternative Lengthening of Telomeres (ALT) is a telomerase-independent pathway that hijacks the homologous recombination pathways to elongate telomeres. Commitment to ALT is often associated with several hallmarks including long telomeres of heterogenous lengths, mutations in histone H3.3 or the ATRX/DAXX histone chaperone complex, and incorporation of non-canonical telomere sequences. The consequences of these genetic and epigenetic changes include enhanced replication stress and the presence of transcriptionally permissive chromatin, which can result in replication-associated DNA damage. Here, we detail the molecular mechanisms that are critical to repairing DNA damage at ALT telomeres, including the BLM Helicase, which acts at several steps in the ALT process. Furthermore, we discuss the emerging findings related to the telomere-associated RNA, TERRA, and its roles in maintaining telomeric integrity. Finally, we review new evidence for therapeutic interventions for ALT-positive cancers which are rooted in understanding the molecular underpinnings of this process.

Indexed as

TelomeraseTelomere HomeostasisChromatinHistonesTelomereChromatinHistonesTelomeraseALTCancerChromatinTelomereTERRA

Identifiers

PMID35588569
PMCPMC9675980
OpenAlexW4280627303

What OpenQuestion holds

Textmetadata
LicenceTDM
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.