Evidence map›Paper›PMID 36807739›Full record

ArticleNucleic acids research2023

The importance of nuclear RAGE-Mcm2 axis in diabetes or cancer-associated replication stress.

Zhe Han, Martin Andrš, Bindhu K Madhavan, Serap Kaymak, Alba Sulaj, Zoltan Kender, Stefan Kopf, Lars Kihm, Rainer Pepperkok, Pavel Janscak and 2 more

Open access · goldAbstract read
In one paragraph

Article in Nucleic acids research, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
1.5field-weighted citation impact, top 19% 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

3 citing papers in PubMed, 8 citations in OpenAlex.

  1. Article
  2. Article
  3. The role of DNA damage in diabetic complications.Nature reviews. Endocrinology · 2024
    Article
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 3 institutions in 3 countries.

Zhe HanDepartment of Medicine I and Clinical Chemistry, University Hospital of Heidelberg, INF 410, Heidelberg, Germany.
Martin AndršInstitute of Molecular Genetics, Academy of Sciences of the Czech Republic, CZ-14300 Prague, Czech Republic.
Bindhu K MadhavanDepartment of Medicine I and Clinical Chemistry, University Hospital of Heidelberg, INF 410, Heidelberg, Germany.
Serap KaymakDepartment of Medicine I and Clinical Chemistry, University Hospital of Heidelberg, INF 410, Heidelberg, Germany.
Alba SulajDepartment of Medicine I and Clinical Chemistry, University Hospital of Heidelberg, INF 410, Heidelberg, Germany.ORCID 0000-0002-6051-6696
Zoltan KenderDepartment of Medicine I and Clinical Chemistry, University Hospital of Heidelberg, INF 410, Heidelberg, Germany.
Stefan KopfDepartment of Medicine I and Clinical Chemistry, University Hospital of Heidelberg, INF 410, Heidelberg, Germany.
Lars KihmDepartment of Medicine I and Clinical Chemistry, University Hospital of Heidelberg, INF 410, Heidelberg, Germany.
Rainer PepperkokEuropean Molecular Biology Laboratory, Advanced Light Microscopy Facility, Heidelberg, Germany.
Pavel JanscakInstitute of Molecular Genetics, Academy of Sciences of the Czech Republic, CZ-14300 Prague, Czech Republic.ORCID 0000-0002-1748-7789
Peter NawrothDepartment of Medicine I and Clinical Chemistry, University Hospital of Heidelberg, INF 410, Heidelberg, Germany.
Varun KumarDepartment of Medicine I and Clinical Chemistry, University Hospital of Heidelberg, INF 410, Heidelberg, Germany.ORCID 0000-0003-2827-1024
Heidelberg University · DECzech Academy of Sciences · CZEuropean Molecular Biology Laboratory · DE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

An elevated frequency of DNA replication defects is associated with diabetes and cancer. However, data linking these nuclear perturbations to the onset or progression of organ complications remained unexplored. Here, we report that RAGE (Receptor for Advanced Glycated Endproducts), previously believed to be an extracellular receptor, upon metabolic stress localizes to the damaged forks. There it interacts and stabilizes the minichromosome-maintenance (Mcm2-7) complex. Accordingly, RAGE deficiency leads to slowed fork progression, premature fork collapse, hypersensitivity to replication stress agents and reduction of viability, which was reversed by the reconstitution of RAGE. This was marked by the 53BP1/OPT-domain expression and the presence of micronuclei, premature loss-of-ciliated zones, increased incidences of tubular-karyomegaly, and finally, interstitial fibrosis. More importantly, the RAGE-Mcm2 axis was selectively compromised in cells expressing micronuclei in human biopsies and mouse models of diabetic nephropathy and cancer. Thus, the functional RAGE-Mcm2/7 axis is critical in handling replication stress in vitro and human disease.

Indexed as

Diabetes MellitusMinichromosome Maintenance Complex Component 2NeoplasmsReceptor for Advanced Glycation End ProductsAnimalsCell Cycle ProteinsDNA ReplicationHumansMiceMinichromosome Maintenance ProteinsCell Cycle ProteinsMCM2 protein, humanMinichromosome Maintenance Complex Component 2Minichromosome Maintenance ProteinsReceptor for Advanced Glycation End Products

Identifiers

PMID36807739
PMCPMC10018352
OpenAlexW4321478526

What OpenQuestion holds

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LicenceCC BY-NC
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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.