Evidence map›Paper›PMID 34819065›Full record

ArticleJournal of biomedical science2021

Elp1 facilitates RAD51-mediated homologous recombination repair via translational regulation.

Wei-Ting Chen, Huan-Yi Tseng, Chung-Lin Jiang, Chih-Ying Lee, Peter Chi, Liuh-Yow Chen, Kai-Yin Lo, I-Ching Wang, Fu-Jung Lin

Open access · diamondAbstract read
In one paragraph

Article in Journal of biomedical science, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.

0numbers the graph read from it
0cells of the map it votes in
9citing papers in PubMed
0.6field-weighted citation impact, top 32% 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

9 citing papers in PubMed, 12 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

9 authors at 4 institutions in 1 country.

Wei-Ting ChenDepartment of Biochemical Science and Technology, National Taiwan University, No.1, Sec.4, Roosevelt Rd., Taipei, 10617, Taiwan.
Huan-Yi TsengDepartment of Biochemical Science and Technology, National Taiwan University, No.1, Sec.4, Roosevelt Rd., Taipei, 10617, Taiwan.
Chung-Lin JiangDepartment of Biochemical Science and Technology, National Taiwan University, No.1, Sec.4, Roosevelt Rd., Taipei, 10617, Taiwan.
Chih-Ying LeeInstitute of Biochemical Sciences, National Taiwan University, Taipei, 10617, Taiwan.
Peter ChiInstitute of Biochemical Sciences, National Taiwan University, Taipei, 10617, Taiwan.
Liuh-Yow ChenInstitute of Molecular Biology, Academia Sinica, Taipei, 11529, Taiwan.
Kai-Yin LoDepartment of Agricultural Chemistry, National Taiwan University, Taipei, 10617, Taiwan.
I-Ching WangInstitute of Biotechnology, National Tsing Hua University, Hsinchu, 30013, Taiwan.
Fu-Jung LinDepartment of Biochemical Science and Technology, National Taiwan University, No.1, Sec.4, Roosevelt Rd., Taipei, 10617, Taiwan. fujlin@ntu.edu.tw.ORCID http://orcid.org/0000-0003-4065-0983
National Taiwan University · TWInstitute of Molecular Biology, Academia Sinica · TWNational Taipei University of Technology · TWNational Tsing Hua University · TW

Funding

Ministry of Science and Technology, Taiwan MOST 104-2320-B-002-040-Ministry of Science and Technology, Taiwan MOST 107-2320-B-002-004-MY3Ministry of Science and Technology, Taiwan MOST 108-2321-B-002-054Ministry of Science and Technology, Taiwan MOST 108-2628-B-001-006
6 · The paper itself

Abstract

backgroundRAD51-dependent homologous recombination (HR) is one of the most important pathways for repairing DNA double-strand breaks (DSBs), and its regulation is crucial to maintain genome integrity. Elp1 gene encodes IKAP/ELP1, a core subunit of the Elongator complex, which has been implicated in translational regulation. However, how ELP1 contributes to genome maintenance is unclear.

methodsTo investigate the function of Elp1, Elp1-deficient mouse embryonic fibroblasts (MEFs) were generated. Metaphase chromosome spreading, immunofluorescence, and comet assays were used to access chromosome abnormalities and DSB formation. Functional roles of Elp1 in MEFs were evaluated by cell viability, colony forming capacity, and apoptosis assays. HR-dependent DNA repair was assessed by reporter assay, immunofluorescence, and western blot. Polysome profiling was used to evaluate translational efficiency. Differentially expressed proteins and signaling pathways were identified using a label-free liquid chromatography-tandem mass spectrometry (LC-MS/MS) proteomics approach.

resultsHere, we report that Elp1 depletion enhanced genomic instability, manifested as chromosome breakage and genotoxic stress-induced genomic DNA fragmentation upon ionizing radiation (IR) exposure. Elp1-deficient cells were hypersensitive to DNA damage and exhibited impaired cell proliferation and defective HR repair. Moreover, Elp1 depletion reduced the formation of IR-induced RAD51 foci and decreased RAD51 protein levels. Polysome profiling analysis revealed that ELP1 regulated RAD51 expression by promoting its translation in response to DNA damage. Notably, the requirement for ELP1 in DSB repair could be partially rescued in Elp1-deficient cells by reintroducing RAD51, suggesting that Elp1-mediated HR-directed repair of DSBs is RAD51-dependent. Finally, using proteome analyses, we identified several proteins involved in cancer pathways and DNA damage responses as being differentially expressed upon Elp1 depletion.

conclusionsOur study uncovered a molecular mechanism underlying Elp1-mediated regulation of HR activity and provides a novel link between translational regulation and genome stability.

Indexed as

Chromosome BreakageAnimalsDNA DamageFibroblastsGenomic InstabilityIntracellular Signaling Peptides and ProteinsMiceProtein BiosynthesisRad51 RecombinaseRecombinational DNA RepairIkbkap protein, mouseIntracellular Signaling Peptides and ProteinsRad51 protein, mouseRad51 RecombinaseDNA damageElp1Homologous recombinationRAD51Translational regulation

Identifiers

PMID34819065
PMCPMC8613991
OpenAlexW3216200902

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.