Evidence map›Paper›PMID 28049724›Full record

ArticleThe Journal of biological chemistry2017

Endonuclease EEPD1 Is a Gatekeeper for Repair of Stressed Replication Forks.

Hyun-Suk Kim, Jac A Nickoloff, Yuehan Wu, Elizabeth A Williamson, Gurjit Singh Sidhu, Brian L Reinert, Aruna S Jaiswal, Gayathri Srinivasan, Bhavita Patel, Kimi Kong and 3 more

Open access · hybridAbstract read
In one paragraph

Article in The Journal of biological chemistry, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.

0numbers the graph read from it
0cells of the map it votes in
30citing papers in PubMed
1.9field-weighted citation impact, top 14% 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

30 citing papers in PubMed, 56 citations in OpenAlex.

  1. Article
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  8. Cellular Responses to Widespread DNA Replication Stress.International journal of molecular sciences · 2023
    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

13 authors at 5 institutions in 1 country.

Hyun-Suk KimFrom the Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis, Indiana 46202.
Jac A Nickoloffthe Department of Environmental and Radiological Health Sciences, Colorado State University, Fort Collins, Colorado 80523.
Yuehan Wuthe Department of Medicine and the Cancer Center, University of Florida Health, Gainesville, Florida 32610, and.
Elizabeth A Williamsonthe Department of Medicine and the Cancer Center, University of Florida Health, Gainesville, Florida 32610, and.
Gurjit Singh Sidhuthe Department of Medicine and the Cancer Center, University of Florida Health, Gainesville, Florida 32610, and.
Brian L Reinertthe Department of Medicine and the Cancer Center, University of Florida Health, Gainesville, Florida 32610, and.
Aruna S Jaiswalthe Department of Medicine and the Cancer Center, University of Florida Health, Gainesville, Florida 32610, and.
Gayathri Srinivasanthe Department of Medicine and the Cancer Center, University of Florida Health, Gainesville, Florida 32610, and.
Bhavita Patelthe Department of Medicine and the Cancer Center, University of Florida Health, Gainesville, Florida 32610, and.
Kimi Kongthe Department of Medicine and the Cancer Center, University of Florida Health, Gainesville, Florida 32610, and.
Sandeep Burmathe Department of Radiation Oncology, University of Texas Southwestern Medical Center, Dallas, Texas 75390.
Suk-Hee LeeFrom the Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis, Indiana 46202, slee@iupui.edu.
Robert A Hromasthe Department of Medicine and the Cancer Center, University of Florida Health, Gainesville, Florida 32610, and robert.hromas@medicine.ufl.edu.
University of Florida Health · USColorado State University · USIndiana University – Purdue University Indianapolis · USIndiana University School of MedicineThe University of Texas Southwestern Medical Center · 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
Molecular mechanisms of GBM radioresistance and strategies for radiosensitizationR01CA149461 · NCI · UT SOUTHWESTERN MEDICAL CENTER · PI BURMA, SANDEEP · 2011 to 2015
$1.6M
Non-Homologous End Joining Repair in HumansR01CA151367 · NCI · INDIANA UNIVERSITY INDIANAPOLIS · PI LEE, SUK-HEE · 2011 to 2015
$1.6M
Mechanisms of EXO1 regulation in response to radiation-induced DNA damageR01CA197796 · NCI · UT SOUTHWESTERN MEDICAL CENTER · PI BURMA, SANDEEP · 2016 to 2020
$1.6M
EPIGENETIC CONTROL OF NHEJ DNA REPAIRR01CA139429 · NCI · UNIVERSITY OF NEW MEXICO · PI HROMAS, ROBERT A · 2010 to 2014
$1.5M
Biomarkers For BRCA1-Deficient CancersR01CA279971 · NCI · UNIVERSITY OF TEXAS HLTH SCIENCE CENTER · PI Kimi Y Kong · 2024 to 2026
$1.3M
Mechanisms for Chromosomal TranslocationsR01GM109645 · NIGMS · UNIVERSITY OF TEXAS HLTH SCIENCE CENTER · PI HROMAS, ROBERT A · 2015 to 2018
$1.2M
Augmented homologous recombination as a mechanism of acquired temozolomide resistance in glioblastomaR21CA202403 · NCI · UT SOUTHWESTERN MEDICAL CENTER · PI BURMA, SANDEEP · 2016 to 2017
$388k
NCI NIH HHS R01 CA139429NCI NIH HHS R01 CA149461NCI NIH HHS R01 CA151367NCI NIH HHS R01 CA197796NCI NIH HHS R01 CA205224NCI NIH HHS R01 CA279971NCI NIH HHS R21 CA202403NIGMS NIH HHS R01 GM084020NIGMS NIH HHS R01 GM109645
6 · The paper itself

Abstract

Replication is not as continuous as once thought, with DNA damage frequently stalling replication forks. Aberrant repair of stressed replication forks can result in cell death or genome instability and resulting transformation to malignancy. Stressed replication forks are most commonly repaired via homologous recombination (HR), which begins with 5' end resection, mediated by exonuclease complexes, one of which contains Exo1. However, Exo1 requires free 5'-DNA ends upon which to act, and these are not commonly present in non-reversed stalled replication forks. To generate a free 5' end, stalled replication forks must therefore be cleaved. Although several candidate endonucleases have been implicated in cleavage of stalled replication forks to permit end resection, the identity of such an endonuclease remains elusive. Here we show that the 5'-endonuclease EEPD1 cleaves replication forks at the junction between the lagging parental strand and the unreplicated DNA parental double strands. This cleavage creates the structure that Exo1 requires for 5' end resection and HR initiation. We observed that EEPD1 and Exo1 interact constitutively, and Exo1 repairs stalled replication forks poorly without EEPD1. Thus, EEPD1 performs a gatekeeper function for replication fork repair by mediating the fork cleavage that permits initiation of HR-mediated repair and restart of stressed forks.

Indexed as

DNA RepairDNA ReplicationEndodeoxyribonucleasesHEK293 CellsHumansEEPD1 protein, humanEndodeoxyribonucleasesDNA damageDNA endonucleaseDNA repairDNA replicationend resectionhomologous recombinationnucleasereplication fork stress

Identifiers

PMID28049724
PMCPMC5314175
OpenAlexW2564606182

What OpenQuestion holds

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LicenceCC BY
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.