Evidence map›Paper›PMID 34070855›Full record

ArticleInternational journal of molecular sciences2021

LEDGF/p75 Is Required for an Efficient DNA Damage Response.

Victoria Liedtke, Christian Schröder, Dirk Roggenbuck, Romano Weiss, Ralf Stohwasser, Peter Schierack, Stefan Rödiger, Lysann Schenk

Open access · goldAbstract read
In one paragraph

Article in International journal of molecular sciences, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.

0numbers the graph read from it
0cells of the map it votes in
18citing papers in PubMed
1.5field-weighted citation impact, top 17% 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

18 citing papers in PubMed, 23 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

8 authors at 1 institution in 1 country.

Victoria LiedtkeFaculty of Natural Sciences, Brandenburg University of Technology Cottbus-Senftenberg, 01968 Senftenberg, Germany.ORCID 0000-0001-7838-5818
Christian SchröderFaculty of Natural Sciences, Brandenburg University of Technology Cottbus-Senftenberg, 01968 Senftenberg, Germany.
Dirk RoggenbuckFaculty of Natural Sciences, Brandenburg University of Technology Cottbus-Senftenberg, 01968 Senftenberg, Germany.ORCID 0000-0002-6861-6827
Romano WeissFaculty of Natural Sciences, Brandenburg University of Technology Cottbus-Senftenberg, 01968 Senftenberg, Germany.
Ralf StohwasserFaculty of Natural Sciences, Brandenburg University of Technology Cottbus-Senftenberg, 01968 Senftenberg, Germany.
Peter SchierackFaculty of Natural Sciences, Brandenburg University of Technology Cottbus-Senftenberg, 01968 Senftenberg, Germany.
Stefan RödigerFaculty of Natural Sciences, Brandenburg University of Technology Cottbus-Senftenberg, 01968 Senftenberg, Germany.ORCID 0000-0002-1441-6512
Lysann SchenkFaculty of Natural Sciences, Brandenburg University of Technology Cottbus-Senftenberg, 01968 Senftenberg, Germany.
Brandenburg University of Technology Cottbus-Senftenberg · DE

Funding

Brandenburger Staatsministerium für Wissenschaft, Forschung und Kultur GeCa: H228-05/002/008, 2017-2019Bundesministerium für Bildung und Forschung 03WKDB2C
6 · The paper itself

Abstract

Lens epithelium-derived growth factor splice variant of 75 kDa (LEDGF/p75) plays an important role in cancer, but its DNA-damage repair (DDR)-related implications are still not completely understood. Different LEDGF model cell lines were generated: a complete knock-out of LEDGF (KO) and re-expression of LEDGF/p75 or LEDGF/p52 using CRISPR/Cas9 technology. Their proliferation and migration capacity as well as their chemosensitivity were determined, which was followed by investigation of the DDR signaling pathways by Western blot and immunofluorescence. LEDGF-deficient cells exhibited a decreased proliferation and migration as well as an increased sensitivity toward etoposide. Moreover, LEDGF-depleted cells showed a significant reduction in the recruitment of downstream DDR-related proteins such as replication protein A 32 kDa subunit (RPA32) after exposure to etoposide. The re-expression of LEDGF/p75 rescued all knock-out effects. Surprisingly, untreated LEDGF KO cells showed an increased amount of DNA fragmentation combined with an increased formation of γH2AX and BRCA1. In contrast, the protein levels of ubiquitin-conjugating enzyme UBC13 and nuclear proteasome activator PA28γ were substantially reduced upon LEDGF KO. This study provides for the first time an insight that LEDGF is not only involved in the recruitment of CtIP but has also an effect on the ubiquitin-dependent regulation of DDR signaling molecules and highlights the role of LEDGF/p75 in homology-directed DNA repair.

Indexed as

Gene Expression RegulationRecombinational DNA RepairAdaptor Proteins, Signal TransducingAntineoplastic Agents, PhytogenicAutoantigensBRCA1 ProteinCell LineCell Line, TumorCell MovementCell ProliferationCRISPR-Cas SystemsDNADNA DamageEpithelial CellsEtoposideGene Knockout TechniquesAdaptor Proteins, Signal TransducingAntineoplastic Agents, PhytogenicAutoantigensBRCA1 ProteinBRCA1 protein, humanDNAEtoposideH2AX protein, humanHistonesKi antigenProteasome Endopeptidase ComplexPSIP1 protein, humanReplication Protein ARPA2 protein, humanTranscription FactorsUBE2N protein, humanUbiquitin-Conjugating EnzymesCRISPR/Cas9DNA damage signalingLEDGFubiquitinationγH2AX

Identifiers

PMID34070855
PMCPMC8198318
OpenAlexW3116555809

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.