Evidence map›Paper›PMID 24651433›Full record

ArticleCell death & disease2014

Homozygous mutation of MTPAP causes cellular radiosensitivity and persistent DNA double-strand breaks.

N T Martin, K Nakamura, U Paila, J Woo, C Brown, J A Wright, S N Teraoka, S Haghayegh, D McCurdy, M Schneider and 4 more

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

Article in Cell death & disease, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.

0numbers the graph read from it
0cells of the map it votes in
12citing papers in PubMed
0.3field-weighted citation impact, top 42% 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

12 citing papers in PubMed, 16 citations in OpenAlex.

  1. Review
  2. Article
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  8. Review
  9. Terminal nucleotidyl transferases (TENTs) in mammalian RNA metabolism.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2018
    Review
  10. Article
  11. Identification of ATIC as a Novel Target for Chemoradiosensitization.International journal of radiation oncology, biology, physics · 2018
    Article
  12. Article
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

14 authors at 6 institutions in 1 country.

N T Martin1] UCLA Department of Pathology and Laboratory Medicine, MacDonald Research Laboratories, Los Angeles, CA, USA [2] UCLA Biomedical Physics Interdepartmental Graduate Program, Los Angeles, CA, USA.
K NakamuraUCLA Department of Pathology and Laboratory Medicine, MacDonald Research Laboratories, Los Angeles, CA, USA.
U PailaDepartment of Public Health Sciences, Center for Public Health Genomics, University of Virginia, Charlottesville, VA, USA.
J WooUCLA Department of Pathology and Laboratory Medicine, MacDonald Research Laboratories, Los Angeles, CA, USA.
C BrownUCLA Department of Pathology and Laboratory Medicine, MacDonald Research Laboratories, Los Angeles, CA, USA.
J A WrightGenetics Institute, University of Florida, Gainesville, FL, USA.
S N TeraokaGenetics Institute, University of Florida, Gainesville, FL, USA.
S HaghayeghUCLA Department of Pathology and Laboratory Medicine, MacDonald Research Laboratories, Los Angeles, CA, USA.
D McCurdyUCLA Department of Pediatrics, Los Angeles, CA, USA.
M SchneiderCarle Physician Group, Urbana, IL, USA.
H HuUCLA Department of Pathology and Laboratory Medicine, MacDonald Research Laboratories, Los Angeles, CA, USA.
A R QuinlanDepartment of Public Health Sciences, Center for Public Health Genomics, University of Virginia, Charlottesville, VA, USA.
R A Gatti1] UCLA Department of Pathology and Laboratory Medicine, MacDonald Research Laboratories, Los Angeles, CA, USA [2] UCLA Biomedical Physics Interdepartmental Graduate Program, Los Angeles, CA, USA [3] UCLA Department of Human Genetics, Los Angeles, CA, USA.
P Concannon1] Genetics Institute, University of Florida, Gainesville, FL, USA [2] Department of Pathology, Immunology and Laboratory Medicine, University of Florida, Gainesville, FL, USA.
University of Florida · USOffice of Public Health Genomics · USUCLA Health · USUniversity of California, Los Angeles · USUniversity of Virginia · USUrbana University · US

Funding

Women's CancersP30CA016042 · NCI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI Samuel Wheeler French · 1985 to 2026
$134.5M
Virology CoreP30AI028697 · NIAID · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI ANTON, PETER A · 1991 to 2018
$39.9M
New algorithms and tools for large-scale genomic analysesR01HG006693 · NHGRI · UNIVERSITY OF VIRGINIA · PI QUINLAN, AARON R · 2012 to 2018
$3.1M
Identification of radiation sensitivity alleles by whole exome sequencingR21ES020521 · NIEHS · UNIVERSITY OF VIRGINIA · PI CONCANNON, PATRICK · 2011 to 2012
$432k
NCI NIH HHS CA-16042NCI NIH HHS P30 CA016042NHGRI NIH HHS R01 HG006693NIAID NIH HHS AI-28697NIAID NIH HHS P30 AI028697NIEHS NIH HHS R21 ES020521
6 · The paper itself

Abstract

The study of rare human syndromes characterized by radiosensitivity has been instrumental in identifying novel proteins and pathways involved in DNA damage responses to ionizing radiation. In the present study, a mutation in mitochondrial poly-A-polymerase (MTPAP), not previously recognized for its role in the DNA damage response, was identified by exome sequencing and subsequently associated with cellular radiosensitivity. Cell lines derived from two patients with the homozygous MTPAP missense mutation were radiosensitive, and this radiosensitivity could be abrogated by transfection of wild-type mtPAP cDNA into mtPAP-deficient cell lines. Further analysis of the cellular phenotype revealed delayed DNA repair, increased levels of DNA double-strand breaks, increased reactive oxygen species (ROS), and increased cell death after irradiation (IR). Pre-IR treatment of cells with the potent anti-oxidants, α-lipoic acid and n-acetylcysteine, was sufficient to abrogate the DNA repair and clonogenic survival defects. Our results firmly establish that mutation of the MTPAP gene results in a cellular phenotype of increased DNA damage, reduced repair kinetics, increased cell death by apoptosis, and reduced clonogenic survival after exposure to ionizing radiation, suggesting a pathogenesis that involves the disruption of ROS homeostasis.

Indexed as

DNA Breaks, Double-StrandedHomozygoteMutation, MissenseAmishAntioxidantsApoptosisCell LineCell SurvivalCytoprotectionDNA-Directed RNA PolymerasesDNA RepairDose-Response Relationship, RadiationGenotypeHumansKineticsLymphocytesAntioxidantsDNA-Directed RNA PolymerasesMitochondrial ProteinsMTPAP protein, humanReactive Oxygen Species

Identifiers

PMID24651433
PMCPMC3973239
OpenAlexW1973944107

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-SA
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.