Evidence map›Paper›PMID 35751457›Full record

ArticleBioEssays : news and reviews in molecular, cellular and developmental biology2022

WRN rescues replication forks compromised by a BRCA2 deficiency: Predictions for how inhibition of a helicase that suppresses premature aging tilts the balance to fork demise and chromosomal instability in cancer.

Arindam Datta, Robert M Brosh

Open access · greenAbstract read
In one paragraph

Article in BioEssays : news and reviews in molecular, cellular and developmental biology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.

0numbers the graph read from it
0cells of the map it votes in
7citing papers in PubMed
0.7field-weighted citation impact, top 33% 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

7 citing papers in PubMed, 9 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

2 authors at 1 institution in 1 country.

Arindam DattaHelicases and Genomic Integrity Section, Translational Gerontology Branch, National Institute on Aging, NIH, Baltimore, Maryland, USA.
Robert M BroshHelicases and Genomic Integrity Section, Translational Gerontology Branch, National Institute on Aging, NIH, Baltimore, Maryland, USA.
National Institute on Aging · US

Funding

Roles Of DNA Helicases In Pathways Required For Maintenance Of Genomic StabilityZIAAG000741 · NIA · NATIONAL INSTITUTE ON AGING · PI BROSH, ROBERT · 2009 to 2025
$7.6M
Model Genetic Systems to Study DNA RepairZIAAG000752 · NIA · NATIONAL INSTITUTE ON AGING · PI BROSH, ROBERT · 2009 to 2025
$4.8M
Intramural NIH HHS ZIA AG000741NIA NIH HHS AG000741
6 · The paper itself

Abstract

Hereditary breast and ovarian cancers are frequently attributed to germline mutations in the tumor suppressor genes BRCA1 and BRCA2. BRCA1/2 act to repair double-strand breaks (DSBs) and suppress the demise of unstable replication forks. Our work elucidated a dynamic interplay between BRCA2 and the WRN DNA helicase/exonuclease defective in the premature aging disorder Werner syndrome. WRN and BRCA2 participate in complementary pathways to stabilize replication forks in cancer cells, allowing them to proliferate. Whether the functional overlap of WRN and BRCA2 is relevant to replication at gaps between newly synthesized DNA fragments, protection of telomeres, and/or metabolism of secondary DNA structures remain to be determined. Advances in understanding the mechanisms elicited during replication stress have prompted the community to reconsider avenues for cancer therapy. Insights from studies of PARP or topoisomerase inhibitors provide working models for the investigation of WRN's mechanism of action. We discuss these topics, focusing on the implications of the WRN-BRCA2 genetic interaction under conditions of replication stress.

Indexed as

Aging, PrematureDNA ReplicationNeoplasmsWerner SyndromeBRCA2 ProteinChromosomal InstabilityDNA HelicasesExodeoxyribonucleasesHumansWerner Syndrome HelicaseBRCA2 ProteinBRCA2 protein, humanDNA HelicasesExodeoxyribonucleasesWerner Syndrome HelicaseWRN protein, humanagingBRCA2cancerDNA repairgenetic diseasegenomic instabilityreplication stresssynthetic lethalityWRN

Identifiers

PMID35751457
PMCPMC9527950
OpenAlexW4283518783

What OpenQuestion holds

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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.