Evidence map›Paper›PMID 33338401›Full record

ArticleMolecular cell2020

A Surge of DNA Damage Links Transcriptional Reprogramming and Hematopoietic Deficit in Fanconi Anemia.

Xi Shen, Rui Wang, Moon Jong Kim, Qianghua Hu, Chih-Chao Hsu, Jun Yao, Naeh Klages-Mundt, Yanyan Tian, Erica Lynn, Thomas F Brewer and 12 more

Open access · bronzeAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Molecular cell, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.

0numbers the graph read from it
0cells of the map it votes in
24citing papers in PubMed
2.5field-weighted citation impact, top 10% 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

24 citing papers in PubMed, 50 citations in OpenAlex.

  1. Review
  2. Review
  3. Article
  4. Article
  5. Article
  6. Article
  7. Differential expression of a disease-associatedbioRxiv : the preprint server for biology · 2025
    Article
  8. Article
  9. Article
  10. Review
  11. Article
  12. Article
  13. Article
  14. Review
  15. Article
  16. [Research progress of Fanconi anemia and DNA interstrand crosslink repair].Zhonghua xue ye xue za zhi = Zhonghua xueyexue zazhi · 2022
    Article
  17. Article
  18. DNA damage and repair in the hematopoietic system.Acta biochimica et biophysica Sinica · 2022
    Review
  19. Article
  20. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

22 authors at 4 institutions in 3 countries.

Xi ShenDepartment of Experimental Radiation Oncology, the University of Texas, MD Anderson Cancer, Houston, TX 77030, USA.
Rui WangDepartment of Experimental Radiation Oncology, the University of Texas, MD Anderson Cancer, Houston, TX 77030, USA.
Moon Jong KimDepartment of Experimental Radiation Oncology, the University of Texas, MD Anderson Cancer, Houston, TX 77030, USA.
Qianghua HuDepartment of Experimental Radiation Oncology, the University of Texas, MD Anderson Cancer, Houston, TX 77030, USA.
Chih-Chao HsuDepartment of Epigenetics and Molecular Carcinogenesis, the University of Texas, MD Anderson Cancer, Houston, TX 77030, USA.
Jun YaoDepartment of Molecular Oncology, the University of Texas, MD Anderson Cancer, Houston, TX 77030, USA.
Naeh Klages-MundtDepartment of Experimental Radiation Oncology, the University of Texas, MD Anderson Cancer, Houston, TX 77030, USA.
Yanyan TianDepartment of Experimental Radiation Oncology, the University of Texas, MD Anderson Cancer, Houston, TX 77030, USA.
Erica LynnDepartment of Experimental Radiation Oncology, the University of Texas, MD Anderson Cancer, Houston, TX 77030, USA.
Thomas F BrewerDepartment of Chemistry, Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA 94720, USA.
Yilei ZhangDepartment of Experimental Radiation Oncology, the University of Texas, MD Anderson Cancer, Houston, TX 77030, USA.
Banu ArunDepartment of Breast Medical Oncology, the University of Texas, MD Anderson Cancer, Houston, TX 77030, USA.
Boyi GanDepartment of Experimental Radiation Oncology, the University of Texas, MD Anderson Cancer, Houston, TX 77030, USA.
Michael AndreeffDepartment of Leukemia, the University of Texas, MD Anderson Cancer, Houston, TX 77030, USA.
Shunichi TakedaDepartment of Radiation Biology, Kyoto University, 606-8501 Kyoto, Japan.
Junjie ChenDepartment of Experimental Radiation Oncology, the University of Texas, MD Anderson Cancer, Houston, TX 77030, USA.
Jae-Il ParkDepartment of Experimental Radiation Oncology, the University of Texas, MD Anderson Cancer, Houston, TX 77030, USA.
Xiaobing ShiDepartment of Epigenetics and Molecular Carcinogenesis, the University of Texas, MD Anderson Cancer, Houston, TX 77030, USA.
Christopher J ChangDepartment of Chemistry, Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA 94720, USA.
Sung Yun JungDepartment of Biochemistry, Baylor College of Medicine, Houston, TX 77030, USA.
Jun QinDepartment of Biochemistry, Baylor College of Medicine, Houston, TX 77030, USA.
Lei LiDepartment of Experimental Radiation Oncology, the University of Texas, MD Anderson Cancer, Houston, TX 77030, USA; Life Sciences Institute, Zhejiang University, Hangzhou 310058, China. Electronic address: leili852002@yahoo.com.
The University of Texas MD Anderson Cancer Center · USBaylor College of Medicine · USUniversity of California, Berkeley · USKyoto University · JP

Funding

Tumor Evolution and Metastasis ProgramP30CA016672 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI Fabien Delerue · 1985 to 2026
$290.8M
Training CoreP42ES004705 · NIEHS · UNIVERSITY OF CALIFORNIA BERKELEY · PI MCHALE, CLIONA · 1987 to 2025
$74.6M
Project 4: Coordinating Nucleolytic Pathways During Crosslink RepairP01CA193124 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI WOOD, RICHARD D · 2017 to 2022
$9.6M
Univ of Calif Berkeley Chemistry-Biology Interface ProgramT32GM066698 · NIGMS · UNIVERSITY OF CALIFORNIA BERKELEY · PI CHANG, CHRISTOPHER J., FRANCIS, MATTHEW B · 2004 to 2023
$7.5M
Chemical Probes to Study Formaldehyde BiologyR01ES028096 · NIEHS · UNIVERSITY OF CALIFORNIA BERKELEY · PI Christopher J. Chang · 2017 to 2026
$4.1M
Role of GAS41 in Human CancerR01CA204020 · NCI · VAN ANDEL RESEARCH INSTITUTE · PI SHI, XIAOBING · 2016 to 2020
$2.0M
Fanconi anemia pathway in DNA damage repairR01CA157448 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI CHEN, JUNJIE · 2012 to 2016
$1.6M
Genetic Framework and Molecular Mechanism of Fanconi AnemiaR01CA190635 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI LI, LEI · 2015 to 2018
$1.5M
Howard Hughes Medical InstituteNCI NIH HHS P01 CA193124NCI NIH HHS P30 CA016672NCI NIH HHS R01 CA157448NCI NIH HHS R01 CA190635NCI NIH HHS R01 CA204020NIEHS NIH HHS P42 ES004705NIEHS NIH HHS R01 ES028096NIGMS NIH HHS T32 GM066698
6 · The paper itself

Abstract

Impaired DNA crosslink repair leads to Fanconi anemia (FA), characterized by a unique manifestation of bone marrow failure and pancytopenia among diseases caused by DNA damage response defects. As a germline disorder, why the hematopoietic hierarchy is specifically affected is not fully understood. We find that reprogramming transcription during hematopoietic differentiation results in an overload of genotoxic stress, which causes aborted differentiation and depletion of FA mutant progenitor cells. DNA damage onset most likely arises from formaldehyde, an obligate by-product of oxidative protein demethylation during transcription regulation. Our results demonstrate that rapid and extensive transcription reprogramming associated with hematopoietic differentiation poses a major threat to genome stability and cell viability in the absence of the FA pathway. The connection between differentiation and DNA damage accumulation reveals a novel mechanism of genome scarring and is critical to exploring therapies to counteract the aplastic anemia for the treatment of FA patients.

Indexed as

Cell DifferentiationCellular ReprogrammingDNA DamageDNA RepairFanconi AnemiaFormaldehydeGene Expression Regulation, DevelopmentalGenomic InstabilityHematopoietic Stem CellsHematopoietic Stem Cell TransplantationHumansK562 CellsTranscription, GeneticFormaldehydebone marrow failuredifferentiationDNA damageFanconi anemiaformaldehydehematopoiesistranscription reprogramming

Identifiers

PMID33338401
PMCPMC8600940
OpenAlexW3102827672

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.