Evidence map›Paper›PMID 27994036›Full record

ArticleNucleic acids research2017

Microhomology-mediated end joining is activated in irradiated human cells due to phosphorylation-dependent formation of the XRCC1 repair complex.

Arijit Dutta, Bradley Eckelmann, Sanjay Adhikari, Kazi Mokim Ahmed, Shiladitya Sengupta, Arvind Pandey, Pavana M Hegde, Miaw-Sheue Tsai, John A Tainer, Michael Weinfeld and 2 more

Open access · goldAbstract read
In one paragraph

Article in Nucleic acids research, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 68 papers.

0numbers the graph read from it
0cells of the map it votes in
68citing papers in PubMed
4.5field-weighted citation impact, top 5% 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

68 citing papers in PubMed, 84 citations in OpenAlex.

  1. Trial
  2. Review
  3. Article
  4. Article
  5. BRCA1-A and LIG4 complexes mediate ecDNA biogenesis and cancer drug resistance.Proceedings of the National Academy of Sciences of the United States of America · 2026
    Article
  6. Article
  7. Article
  8. Defective Microhomology-Mediated End-joining in SMARCB1-Deficient Tumors.bioRxiv : the preprint server for biology · 2025
    Article
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  10. Review
  11. Article
  12. Review
  13. Article
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  16. Article
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8 more citing papers are in PubMed but not listed here.

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

12 authors at 6 institutions in 2 countries.

Arijit DuttaDepartment of Radiation Oncology, Houston Methodist Research Institute, Houston, TX 77030, USA.
Bradley EckelmannDepartment of Radiation Oncology, Houston Methodist Research Institute, Houston, TX 77030, USA.
Sanjay AdhikariEntroGen, Inc., Woodland Hills, CA 91367, USA.
Kazi Mokim AhmedDepartment of Radiation Oncology, Houston Methodist Research Institute, Houston, TX 77030, USA.
Shiladitya SenguptaDepartment of Radiation Oncology, Houston Methodist Research Institute, Houston, TX 77030, USA.
Arvind PandeyDepartment of Radiation Oncology, Houston Methodist Research Institute, Houston, TX 77030, USA.
Pavana M HegdeDepartment of Radiation Oncology, Houston Methodist Research Institute, Houston, TX 77030, USA.
Miaw-Sheue TsaiDepartment of Cell and Molecular Biology, Lawrence Berkeley National Laboratory (LBNL), Berkeley, CA 94720, USA.
John A TainerDepartment of Cell and Molecular Biology, Lawrence Berkeley National Laboratory (LBNL), Berkeley, CA 94720, USA.
Michael WeinfeldDepartment of Oncology, University of Alberta, Cross Cancer Institute, Edmonton, Alberta T6G 1Z2, Canada.
Muralidhar L HegdeDepartment of Radiation Oncology, Houston Methodist Research Institute, Houston, TX 77030, USA.
Sankar MitraDepartment of Radiation Oncology, Houston Methodist Research Institute, Houston, TX 77030, USA.
Houston Methodist · USTexas A&M Health Science Center · USEntroGen (United States) · USLawrence Berkeley National Laboratory · USThe University of Texas MD Anderson Cancer Center · USUniversity of Alberta · CA

Funding

Transcription-Coupled & Replication-Associated Excision RepairP01CA092584 · NCI · UNIVERSITY OF CALIF-LAWRENC BERKELEY LAB · PI John A. Tainer · 2001 to 2026
$89.6M
Mre11/Rad50 Structural Biology for DNA Damage ResponsesR01CA117638 · NCI · SCRIPPS RESEARCH INSTITUTE, THE · PI RUSSELL, PAUL, TAINER, JOHN A. · 2005 to 2019
$5.6M
Etiological Linkage of DNA Damage/Repair Deficiency in Neurodegenerative DiseasesR01NS088645 · NINDS · METHODIST HOSPITAL RESEARCH INSTITUTE · PI HEGDE, MURALIDHAR L · 2015 to 2019
$1.8M
"Repair Co-ordination of Radiation-Induced Clustered Damage In Mammalian Genomes"R01CA158910 · NCI · UNIVERSITY OF TEXAS MED BR GALVESTON · PI MITRA, SANKAR · 2012 to 2016
$1.6M
Repair of Oxidative Genome Damage Associated with Gene ActivationR01GM105090 · NIGMS · METHODIST HOSPITAL RESEARCH INSTITUTE · PI MITRA, SANKAR · 2014 to 2017
$1.2M
NCI NIH HHS P01 CA092584NCI NIH HHS R01 CA117638NCI NIH HHS R01 CA158910NIGMS NIH HHS R01 GM105090NINDS NIH HHS R01 NS088645
6 · The paper itself

Abstract

Microhomology-mediated end joining (MMEJ), an error-prone pathway for DNA double-strand break (DSB) repair, is implicated in genomic rearrangement and oncogenic transformation; however, its contribution to repair of radiation-induced DSBs has not been characterized. We used recircularization of a linearized plasmid with 3΄-P-blocked termini, mimicking those at X-ray-induced strand breaks, to recapitulate DSB repair via MMEJ or nonhomologous end-joining (NHEJ). Sequence analysis of the circularized plasmids allowed measurement of relative activity of MMEJ versus NHEJ. While we predictably observed NHEJ to be the predominant pathway for DSB repair in our assay, MMEJ was significantly enhanced in preirradiated cells, independent of their radiation-induced arrest in the G2/M phase. MMEJ activation was dependent on XRCC1 phosphorylation by casein kinase 2 (CK2), enhancing XRCC1's interaction with the end resection enzymes MRE11 and CtIP. Both endonuclease and exonuclease activities of MRE11 were required for MMEJ, as has been observed for homology-directed DSB repair (HDR). Furthermore, the XRCC1 co-immunoprecipitate complex (IP) displayed MMEJ activity in vitro, which was significantly elevated after irradiation. Our studies thus suggest that radiation-mediated enhancement of MMEJ in cells surviving radiation therapy may contribute to their radioresistance and could be therapeutically targeted.

Indexed as

DNA End-Joining RepairCasein Kinase IICell Line, TumorDNA-Binding ProteinsDNA Breaks, Double-StrandedHumansPhosphorylationX-ray Repair Cross Complementing Protein 1X-RaysCasein Kinase IIDNA-Binding ProteinsX-ray Repair Cross Complementing Protein 1XRCC1 protein, human

Identifiers

PMID27994036
PMCPMC5389627
OpenAlexW2562288473

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Registered trials

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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.