Evidence map›Paper›PMID 25501596›Full record

ArticleCell death and differentiation2015

PARP-2 sustains erythropoiesis in mice by limiting replicative stress in erythroid progenitors.

J Farrés, L Llacuna, J Martin-Caballero, C Martínez, J J Lozano, C Ampurdanés, A J López-Contreras, L Florensa, J Navarro, E Ottina and 5 more

Open access · bronzeAbstract read
In one paragraph

Article in Cell death and differentiation, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 92 papers, 6 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
92citing papers in PubMed, 6 pooled it
2.1field-weighted citation impact, top 12% 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

92 citing papers in PubMed, 6 syntheses or guidelines pooled it, 168 citations in OpenAlex.

  1. Pooled it
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  13. HM568 Enhances NADMolecular neurobiology · 2026
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  18. Neutropenic events associated with new anticancer treatments, from pathophysiology to practice: a scoping review-NEW Group (Neutropenic Events Working Group).Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer · 2025
    Article
  19. Expert opinion on the management of anemia in prostate cancer patients receiving PARP inhibitors.Canadian Urological Association journal = Journal de l'Association des urologues du Canada · 2025
    Review
  20. Article

32 more citing papers are in PubMed but not listed here.

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

15 authors at 7 institutions in 3 countries.

J FarrésCancer Research Program, Hospital del Mar Medical Research Institute (IMIM), Barcelona, Spain.
L LlacunaCancer Research Program, Hospital del Mar Medical Research Institute (IMIM), Barcelona, Spain.
J Martin-CaballeroBarcelona Biomedical Research Park (PRBB), Barcelona, Spain.
C MartínezCIBERehd, Barcelona, Spain.
J J LozanoCIBERehd, Barcelona, Spain.
C AmpurdanésCancer Research Program, Hospital del Mar Medical Research Institute (IMIM), Barcelona, Spain.
A J López-ContrerasGenomic Instability Group, Spanish National Cancer Research Centre (CNIO), Madrid, Spain.
L Florensa1] Cancer Research Program, Hospital del Mar Medical Research Institute (IMIM), Barcelona, Spain [2] Deparment of Pathology, Hospital del Mar, Barcelona, Spain.
J NavarroCancer Research Program, Hospital del Mar Medical Research Institute (IMIM), Barcelona, Spain.
E OttinaDivision of Developmental Immunology, Biocenter, Innsbruck Medical University, Innsbruck, Austria.
F DantzerBiotechnology and Cell Signaling, UMR7242-CNRS, Laboratory of Excellence Medalis, ESBS, Illkirch, France.
V SchreiberBiotechnology and Cell Signaling, UMR7242-CNRS, Laboratory of Excellence Medalis, ESBS, Illkirch, France.
A VillungerDivision of Developmental Immunology, Biocenter, Innsbruck Medical University, Innsbruck, Austria.
O Fernández-CapetilloGenomic Instability Group, Spanish National Cancer Research Centre (CNIO), Madrid, Spain.
J Yélamos1] Cancer Research Program, Hospital del Mar Medical Research Institute (IMIM), Barcelona, Spain [2] CIBERehd, Barcelona, Spain [3] Department of Immunology, Hospital del Mar, Barcelona, Spain.
Hospital del Mar Research Institute · ESCentre National de la Recherche Scientifique · FRCentro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas · ESInnsbruck Medical University · ATSpanish National Cancer Research Centre · ESBarcelona Biomedical Research Park · ESHospital Del Mar · ES

Funding

Austrian Science Fund FWF I 1298European Research Council 210520Worldwide Cancer Research 12-0229
6 · The paper itself

Abstract

Erythropoiesis is a tightly regulated process in which multipotential hematopoietic stem cells produce mature red blood cells. Here we show that deletion of poly(ADP-ribose) polymerase-2 (PARP-2) in mice leads to chronic anemia at steady state, despite increased erythropoietin plasma levels, a phenomenon not observed in mice lacking PARP-1. Loss of PARP-2 causes shortened lifespan of erythrocytes and impaired differentiation of erythroid progenitors. In erythroblasts, PARP-2 deficiency triggers replicative stress, as indicated by the presence of micronuclei, the accumulation of γ-H2AX (phospho-histone H2AX) in S-phase cells and constitutive CHK1 and replication protein A phosphorylation. Transcriptome analyses revealed the activation of the p53-dependent DNA-damage response pathways in PARP-2-deficient cells, culminating in the upregulation of cell-cycle and cell death regulators, concomitant with G2/M arrest and apoptosis. Strikingly, while loss of the proapoptotic p53 target gene Puma restored hematocrit levels in the PARP-2-deficient mice, loss of the cell-cycle regulator and CDK inhibitor p21 leads to perinatal death by exacerbating impaired fetal liver erythropoiesis in PARP-2-deficient embryos. Although the anemia displayed by PARP-2-deficient mice is compatible with life, mice die rapidly when exposed to stress-induced enhanced hemolysis. Our results pinpoint an essential role for PARP-2 in erythropoiesis by limiting replicative stress that becomes essential in the absence of p21 and in the context of enhanced hemolysis, highlighting the potential effect that might arise from the design and use of PARP inhibitors that specifically inactivate PARP proteins.

Indexed as

DNA ReplicationAnimalsApoptosisErythroid Precursor CellsErythropoiesisG2 Phase Cell Cycle CheckpointsGene DeletionHistonesMicePoly(ADP-ribose) PolymerasesStress, Physiologicalgamma-H2AX protein, mouseHistonesParp2 protein, mousePoly(ADP-ribose) Polymerases

Identifiers

PMID25501596
PMCPMC4568570
OpenAlexW2087949216

What OpenQuestion holds

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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.