Evidence map›Paper›PMID 36480547›Full record

ArticlePLoS genetics2022

RAD18 opposes transcription-associated genome instability through FANCD2 recruitment.

James P Wells, Emily Yun-Chia Chang, Leticia Dinatto, Justin White, Stephanie Ryall, Peter C Stirling

Open access · goldAbstract read
In one paragraph

Article in PLoS genetics, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
11citing papers in PubMed, 1 pooled it
1.0field-weighted citation impact, top 24% 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

11 citing papers in PubMed, 1 synthesis or guideline pooled it, 13 citations in OpenAlex.

  1. Pooled it
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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

6 authors at 2 institutions in 1 country.

James P WellsTerry Fox Laboratory, BC Cancer, Vancouver, Canada.
Emily Yun-Chia ChangTerry Fox Laboratory, BC Cancer, Vancouver, Canada.
Leticia DinattoTerry Fox Laboratory, BC Cancer, Vancouver, Canada.
Justin WhiteTerry Fox Laboratory, BC Cancer, Vancouver, Canada.
Stephanie RyallTerry Fox Laboratory, BC Cancer, Vancouver, Canada.
Peter C StirlingTerry Fox Laboratory, BC Cancer, Vancouver, Canada.ORCID 0000-0003-2651-4539
Terry Fox Research Institute · CAUniversity of British Columbia · CA

Funding

CIHR 398871
6 · The paper itself

Abstract

DNA replication is a vulnerable time for genome stability maintenance. Intrinsic stressors, as well as oncogenic stress, can challenge replication by fostering conflicts with transcription and stabilizing DNA:RNA hybrids. RAD18 is an E3 ubiquitin ligase for PCNA that is involved in coordinating DNA damage tolerance pathways to preserve genome stability during replication. In this study, we show that RAD18 deficient cells have higher levels of transcription-replication conflicts and accumulate DNA:RNA hybrids that induce DNA double strand breaks and replication stress. We find that these effects are driven in part by failure to recruit the Fanconi Anemia protein FANCD2 at difficult to replicate and R-loop prone genomic sites. FANCD2 activation caused by splicing inhibition or aphidicolin treatment is critically dependent on RAD18 activity. Thus, we highlight a RAD18-dependent pathway promoting FANCD2-mediated suppression of R-loops and transcription-replication conflicts.

Indexed as

DNA RepairFanconi AnemiaDNADNA-Binding ProteinsDNA DamageDNA ReplicationFanconi Anemia Complementation Group D2 ProteinGenomic InstabilityHumansRNAUbiquitin-Protein LigasesDNADNA-Binding ProteinsFANCD2 protein, humanFanconi Anemia Complementation Group D2 ProteinRAD18 protein, humanRNAUbiquitin-Protein Ligases

Identifiers

PMID36480547
PMCPMC9767342
OpenAlexW4310881240

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.