Evidence map›Paper›PMID 26900729›Full record

ArticleCell cycle (Georgetown, Tex.)2016

The homologous recombination component EEPD1 is required for genome stability in response to developmental stress of vertebrate embryogenesis.

Changzoon Chun, Yuehan Wu, Suk-Hee Lee, Elizabeth A Williamson, Brian L Reinert, Aruna Shanker Jaiswal, Jac A Nickoloff, Robert A Hromas

Open access · hybridAbstract read
In one paragraph

Article in Cell cycle (Georgetown, Tex.), 2016. 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
0.7field-weighted citation impact, top 26% 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, 40 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Article
  5. Cellular Responses to Widespread DNA Replication Stress.International journal of molecular sciences · 2023
    Review
  6. Article
  7. Review
  8. DNA repair genes play a variety of roles in the development of fish embryos.Frontiers in cell and developmental biology · 2023
    Review
  9. Article
  10. Article
  11. Review
  12. Article
  13. Review
  14. Article
  15. Review
  16. Article
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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 3 institutions in 1 country.

Changzoon Chuna Division of Hematology/Oncology , Department of Medicine, University of Florida Health , Gainesville , FL , USA.
Yuehan Wua Division of Hematology/Oncology , Department of Medicine, University of Florida Health , Gainesville , FL , USA.
Suk-Hee Leeb Department of Biochemistry and Molecular Biology , Indiana University School of Medicine , Indianapolis , IN , USA.
Elizabeth A Williamsona Division of Hematology/Oncology , Department of Medicine, University of Florida Health , Gainesville , FL , USA.
Brian L Reinerta Division of Hematology/Oncology , Department of Medicine, University of Florida Health , Gainesville , FL , USA.
Aruna Shanker Jaiswala Division of Hematology/Oncology , Department of Medicine, University of Florida Health , Gainesville , FL , USA.
Jac A Nickoloffc Department of Environmental and Radiological Health Sciences , Colorado State University , Fort Collins , CO , USA.
Robert A Hromasa Division of Hematology/Oncology , Department of Medicine, University of Florida Health , Gainesville , FL , USA.
University of Florida Health · USColorado State University · USIndiana University – Purdue University Indianapolis · US

Funding

EEPD1 Repair of Stressed Replication ForksR01CA205224 · NCI · UNIVERSITY OF TEXAS HLTH SCIENCE CENTER · PI Robert A Hromas · 2016 to 2026
$3.3M
METNASE ROLES IN NHEJ, DNA INTEGRATION AND TRANSLOCATIONR01GM084020 · NIGMS · COLORADO STATE UNIVERSITY · PI NICKOLOFF, JAC A · 2009 to 2016
$2.4M
Non-Homologous End Joining Repair in HumansR01CA151367 · NCI · INDIANA UNIVERSITY INDIANAPOLIS · PI LEE, SUK-HEE · 2011 to 2015
$1.6M
EPIGENETIC CONTROL OF NHEJ DNA REPAIRR01CA139429 · NCI · UNIVERSITY OF NEW MEXICO · PI HROMAS, ROBERT A · 2010 to 2014
$1.5M
Mechanisms for Chromosomal TranslocationsR01GM109645 · NIGMS · UNIVERSITY OF TEXAS HLTH SCIENCE CENTER · PI HROMAS, ROBERT A · 2015 to 2018
$1.2M
NCI NIH HHS NIH R01 CA139429NCI NIH HHS NIH R01 CA152367NCI NIH HHS R01 CA151367NCI NIH HHS R01 CA205224NIGMS NIH HHS GM109645NIGMS NIH HHS NIH R01 GM084020NIGMS NIH HHS R01 GM084020NIGMS NIH HHS R01 GM109645
6 · The paper itself

Abstract

Stressed replication forks can be conservatively repaired and restarted using homologous recombination (HR), initiated by nuclease cleavage of branched structures at stalled forks. We previously reported that the 5' nuclease EEPD1 is recruited to stressed replication forks, where it plays critical early roles in HR initiation by promoting fork cleavage and end resection. HR repair of stressed replication forks prevents their repair by non-homologous end-joining (NHEJ), which would cause genome instability. Rapid cell division during vertebrate embryonic development generates enormous pressure to maintain replication speed and accuracy. To determine the role of EEPD1 in maintaining replication fork integrity and genome stability during rapid cell division in embryonic development, we assessed the role of EEPD1 during zebrafish embryogenesis. We show here that when EEPD1 is depleted, zebrafish embryos fail to develop normally and have a marked increase in death rate. Zebrafish embryos depleted of EEPD1 are far more sensitive to replication stress caused by nucleotide depletion. We hypothesized that the HR defect with EEPD1 depletion would shift repair of stressed replication forks to unopposed NHEJ, causing chromosome abnormalities. Consistent with this, EEPD1 depletion results in nuclear defects including anaphase bridges and micronuclei in stressed zebrafish embryos, similar to BRCA1 deficiency. These results demonstrate that the newly characterized HR protein EEPD1 maintains genome stability during embryonic replication stress. These data also imply that the rapid cell cycle transit seen during embryonic development produces replication stress that requires HR to resolve.

Indexed as

Genomic InstabilityAnimalsDNA ReplicationEmbryonic DevelopmentEndodeoxyribonucleasesSignal TransductionZebrafishZebrafish ProteinsEEPD1 protein, zebrafishEndodeoxyribonucleasesZebrafish Proteins

Identifiers

PMID26900729
PMCPMC4889227
OpenAlexW2337611083

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.