Evidence map›Paper›PMID 34188037›Full record

ArticleNature communications2021

Non-canonical function of DGCR8 in DNA double-strand break repair signaling and tumor radioresistance.

Qinglei Hang, Liyong Zeng, Li Wang, Litong Nie, Fan Yao, Hongqi Teng, Yalan Deng, Shannon Yap, Yutong Sun, Steven J Frank and 2 more

Open access · goldAbstract read
In one paragraph

Article in Nature communications, 2021. 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
5.8field-weighted citation impact, top 3% 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, 70 citations in OpenAlex.

  1. Review
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  9. Regulation of the microprocessor by post-translational modifications.Frontiers in cell and developmental biology · 2025
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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

12 authors at 1 institution in 2 countries.

Qinglei HangDepartment of Experimental Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.ORCID 0000-0003-0419-6621
Liyong ZengDepartment of Experimental Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Li WangDepartment of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.ORCID 0000-0003-2895-0422
Litong NieDepartment of Experimental Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.ORCID 0000-0002-0326-4517
Fan YaoDepartment of Experimental Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Hongqi TengDepartment of Experimental Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Yalan DengDepartment of Experimental Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.ORCID 0000-0002-3954-3243
Shannon YapDepartment of Experimental Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Yutong SunDepartment of Molecular and Cellular Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Steven J FrankDepartment of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Junjie ChenDepartment of Experimental Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.ORCID 0000-0002-1493-2189
Li MaDepartment of Experimental Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. lma4@mdanderson.org.ORCID 0000-0001-9965-989X
The University of Texas MD Anderson Cancer Center · US

Funding

Tumor Evolution and Metastasis ProgramP30CA016672 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI Fabien Delerue · 1985 to 2026
$290.8M
Regulation of metastasis and epithelial-mesenchymal transition by microRNAsR01CA166051 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI MA, LI · 2012 to 2023
$3.4M
Epithelial-mesenchymal transition regulators in radioresistance and DNA repairR01CA181029 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI MA, LI · 2014 to 2018
$1.7M
NCI NIH HHS P30 CA016672NCI NIH HHS R01 CA166051NCI NIH HHS R01 CA181029
6 · The paper itself

Abstract

In response to DNA double-strand breaks (DSBs), repair proteins are recruited to the damaged sites. Ubiquitin signaling plays a critical role in coordinating protein recruitment during the DNA damage response. Here, we find that the microRNA biogenesis factor DGCR8 promotes tumor resistance to X-ray radiation independently of its Drosha-binding ability. Upon radiation, the kinase ATM and the deubiquitinase USP51 mediate the activation and stabilization of DGCR8 through phosphorylation and deubiquitination. Specifically, radiation-induced ATM-dependent phosphorylation of DGCR8 at serine 677 facilitates USP51 to bind, deubiquitinate, and stabilize DGCR8, which leads to the recruitment of DGCR8 and DGCR8's binding partner RNF168 to MDC1 and RNF8 at DSBs. This, in turn, promotes ubiquitination of histone H2A, repair of DSBs, and radioresistance. Altogether, these findings reveal the non-canonical function of DGCR8 in DSB repair and suggest that radiation treatment may result in therapy-induced tumor radioresistance through ATM- and USP51-mediated activation and upregulation of DGCR8.

Indexed as

DNA Breaks, Double-StrandedAdaptor Proteins, Signal TransducingAtaxia Telangiectasia Mutated ProteinsCell Cycle ProteinsCell Line, TumorDeubiquitinating EnzymesDNA-Binding ProteinsDNA RepairHCT116 CellsHEK293 CellsHeLa CellsHep G2 CellsHistonesHumansMCF-7 CellsNeoplasmsAdaptor Proteins, Signal TransducingAtaxia Telangiectasia Mutated ProteinsATM protein, humanCell Cycle ProteinsDeubiquitinating EnzymesDGCR8 protein, humanDNA-Binding ProteinsHistonesMDC1 protein, humanRNA-Binding ProteinsRNF168 protein, humanRNF8 protein, humanUbiquitin-Protein LigasesUbiquitin-Specific ProteasesUSP51 protein, human

Identifiers

PMID34188037
PMCPMC8242032
OpenAlexW3174800231

What OpenQuestion holds

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LicenceCC BY
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Registered trials

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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.