Evidence map›Paper›PMID 24420907›Full record

ArticleStem cells (Dayton, Ohio)2014

Exonuclease 1 is a critical mediator of survival during DNA double strand break repair in nonquiescent hematopoietic stem and progenitor cells.

Amar Desai, Yulan Qing, Stanton L Gerson

Open access · greenAbstract read
In one paragraph

Article in Stem cells (Dayton, Ohio), 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.

0numbers the graph read from it
0cells of the map it votes in
11citing papers in PubMed
1.2field-weighted citation impact, top 23% 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

11 citing papers in PubMed, 23 citations in OpenAlex.

  1. Novel candidate metastasis-associated genes for synovial sarcoma.Journal of cellular and molecular medicine · 2024
    Article
  2. DNA Damage Responses, the Trump Card of Stem Cells in the Survival Game.Advances in experimental medicine and biology · 2024
    Review
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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

3 authors at 2 institutions in 1 country.

Amar DesaiDepartment of Pharmacology, Case Western Reserve University and University Hospitals Case Medical Center, Cleveland, Ohio, USA; Division of Hematology/Oncology, National Center for Regenerative Medicine, Case Western Reserve University and University Hospitals Case Medical Center, Cleveland, Ohio, USA; Case Comprehensive Cancer Center, Seidman Cancer Center, Case Western Reserve University and University Hospitals Case Medical Center, Cleveland, Ohio, USA.
Yulan Qing
Stanton L Gerson
University Hospitals Seidman Cancer Center · USUniversity Hospitals Case Medical Center · US

Funding

TUMOR METABOLISM PROGRAMP30CA043703 · NCI · CASE WESTERN RESERVE UNIVERSITY · PI MARK R CHANCE · 1987 to 2026
$142.3M
PREDOCTORAL TRAINING PROGRAM IN MOLECULAR THERAPEUTICST32GM008803 · NIGMS · CASE WESTERN RESERVE UNIVERSITY · PI MIEYAL, JOHN J, NIEMAN, MARVIN THOMAS · 2001 to 2023
$4.2M
Lentiviral-MGMT gene transfer into hematopoietic stem cellsR42CA128269 · NCI · LENTIGEN CORPORATION · PI GERSON, STANTON L. · 2010 to 2011
$2.7M
NCI NIH HHS 2P30 CA043703-23NCI NIH HHS 5R42 CA128269-02NCI NIH HHS P30 CA043703NCI NIH HHS R42 CA128269NIGMS NIH HHS 5T32GM008803-10NIGMS NIH HHS T32 GM008803
6 · The paper itself

Abstract

Hematopoietic stem cell (HSC) populations require DNA repair pathways to maintain their long-term survival and reconstitution capabilities, but mediators of these processes are still being elucidated. Exonuclease 1 (Exo1) participates in homologous recombination (HR) and Exo1 loss results in impaired 5' HR end resection. We use cultured Exo1(mut) fibroblasts and bone marrow to demonstrate that loss of Exo1 function results in defective HR in cycling cells. Conversely, in Exo1(mut) mice HR is not required for maintenance of quiescent HSCs at steady state, confirming the steady state HSC reliance on nonhomologous end joining (NHEJ). Exo1(mut) mice sustained serial repopulation, displayed no defect in competitive repopulation or niche occupancy, and exhibited no increased sensitivity to whole body ionizing radiation. However, when Exo1(mut) HSCs were pushed into cell cycle in vivo with 5-fluorouracil or poly IC, the hematopoietic population became hypersensitive to IR, resulting in HSC defects and animal death. We propose Exo1-mediated HR is dispensable for stem cell function in quiescent HSC, whereas it is essential to HSC response to DNA damage processing after cell cycle entry, and its loss is not compensated by intact NHEJ. In HSCs, the maintenance of stem cell function after DNA damage is dependent on the DNA repair capacity, segregated by active versus quiescent points in cell cycle.

Indexed as

AnimalsCell CycleDNA Breaks, Double-StrandedDNA DamageDNA End-Joining RepairExodeoxyribonucleasesFluorouracilHematopoietic Stem CellsHomologous RecombinationMiceStem Cellsexodeoxyribonuclease IExodeoxyribonucleasesFluorouracilCell cycleDNA repairHematopoietic stem cellsHomologous recombination

Identifiers

PMID24420907
PMCPMC4011928
OpenAlexW1592038665

What OpenQuestion holds

Textmetadata
LicenceTDM
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.