Evidence map›Paper›PMID 27989676›Full record

ArticleCurrent biology : CB2017

DNA Damage Follows Repair Factor Depletion and Portends Genome Variation in Cancer Cells after Pore Migration.

Jerome Irianto, Yuntao Xia, Charlotte R Pfeifer, Avathamsa Athirasala, Jiazheng Ji, Cory Alvey, Manu Tewari, Rachel R Bennett, Shane M Harding, Andrea J Liu and 2 more

Open access · bronzeAbstract read
In one paragraph

Article in Current biology : CB, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 181 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
181citing papers in PubMed, 1 pooled it
20.4field-weighted citation impact, top 1% 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

181 citing papers in PubMed, 1 synthesis or guideline pooled it, 302 citations in OpenAlex.

  1. Pooled it
  2. Review
  3. Article
  4. Review
  5. Review
  6. Article
  7. Mechanical regulation of cell memory.Nature structural & molecular biology · 2026
    Review
  8. Article
  9. Article
  10. Article
  11. Article
  12. Article
  13. Review
  14. Article
  15. Article
  16. Cell confinement initiates a delayed but heritable loss of chromosomes.bioRxiv : the preprint server for biology · 2026
    Article
  17. Article
  18. Article
  19. Article
  20. Article

121 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 3 institutions in 1 country.

Jerome IriantoPhysical Sciences Oncology Center at Penn (PSOC@Penn), 129 Towne Building, University of Pennsylvania, Philadelphia, PA 19104, USA; Molecular and Cell Biophysics Lab, 129 Towne Building, University of Pennsylvania, Philadelphia, PA 19104, USA.
Yuntao XiaPhysical Sciences Oncology Center at Penn (PSOC@Penn), 129 Towne Building, University of Pennsylvania, Philadelphia, PA 19104, USA; Molecular and Cell Biophysics Lab, 129 Towne Building, University of Pennsylvania, Philadelphia, PA 19104, USA.
Charlotte R PfeiferPhysical Sciences Oncology Center at Penn (PSOC@Penn), 129 Towne Building, University of Pennsylvania, Philadelphia, PA 19104, USA; Molecular and Cell Biophysics Lab, 129 Towne Building, University of Pennsylvania, Philadelphia, PA 19104, USA; Graduate Group, Department of Physics and Astronomy, 129 Towne Building, University of Pennsylvania, Philadelphia, PA 19104, USA.
Avathamsa AthirasalaMolecular and Cell Biophysics Lab, 129 Towne Building, University of Pennsylvania, Philadelphia, PA 19104, USA.
Jiazheng JiPhysical Sciences Oncology Center at Penn (PSOC@Penn), 129 Towne Building, University of Pennsylvania, Philadelphia, PA 19104, USA; Molecular and Cell Biophysics Lab, 129 Towne Building, University of Pennsylvania, Philadelphia, PA 19104, USA.
Cory AlveyPhysical Sciences Oncology Center at Penn (PSOC@Penn), 129 Towne Building, University of Pennsylvania, Philadelphia, PA 19104, USA; Molecular and Cell Biophysics Lab, 129 Towne Building, University of Pennsylvania, Philadelphia, PA 19104, USA.
Manu TewariPhysical Sciences Oncology Center at Penn (PSOC@Penn), 129 Towne Building, University of Pennsylvania, Philadelphia, PA 19104, USA; Molecular and Cell Biophysics Lab, 129 Towne Building, University of Pennsylvania, Philadelphia, PA 19104, USA.
Rachel R BennettPhysical Sciences Oncology Center at Penn (PSOC@Penn), 129 Towne Building, University of Pennsylvania, Philadelphia, PA 19104, USA; Graduate Group, Department of Physics and Astronomy, 129 Towne Building, University of Pennsylvania, Philadelphia, PA 19104, USA.
Shane M HardingPhysical Sciences Oncology Center at Penn (PSOC@Penn), 129 Towne Building, University of Pennsylvania, Philadelphia, PA 19104, USA; Cancer Biology, Abramson Family Cancer Research Institute, Perelman School of Medicine, 129 Towne Building, University of Pennsylvania, Philadelphia, PA 19104, USA.
Andrea J LiuPhysical Sciences Oncology Center at Penn (PSOC@Penn), 129 Towne Building, University of Pennsylvania, Philadelphia, PA 19104, USA; Graduate Group, Department of Physics and Astronomy, 129 Towne Building, University of Pennsylvania, Philadelphia, PA 19104, USA.
Roger A GreenbergPhysical Sciences Oncology Center at Penn (PSOC@Penn), 129 Towne Building, University of Pennsylvania, Philadelphia, PA 19104, USA; Cancer Biology, Abramson Family Cancer Research Institute, Perelman School of Medicine, 129 Towne Building, University of Pennsylvania, Philadelphia, PA 19104, USA.
Dennis E DischerPhysical Sciences Oncology Center at Penn (PSOC@Penn), 129 Towne Building, University of Pennsylvania, Philadelphia, PA 19104, USA; Molecular and Cell Biophysics Lab, 129 Towne Building, University of Pennsylvania, Philadelphia, PA 19104, USA; Graduate Group, Department of Physics and Astronomy, 129 Towne Building, University of Pennsylvania, Philadelphia, PA 19104, USA. Electronic address: discher@seas.upenn.edu.
Penn Center for AIDS Research · USUniversity of Pennsylvania · USCancer Research Institute · US

Funding

PSOC@Penn Education and OutreachU54CA193417 · NCI · UNIVERSITY OF PENNSYLVANIA · PI DISCHER, DENNIS E. · 2015 to 2020
$10.5M
The RAP80-BRCC36 Deubiquitinating Complex in DNA RepairR01CA138835 · NCI · UNIVERSITY OF PENNSYLVANIA · PI Roger A Greenberg · 2010 to 2026
$5.2M
Roles of Chromatin Modification in BRCA1 Dependent DNA RepairR01CA174904 · NCI · UNIVERSITY OF PENNSYLVANIA · PI Roger A Greenberg · 2013 to 2026
$4.8M
DNA Double Strand Break Chromatin Alterations and Genome IntegrityR01GM101149 · NIGMS · UNIVERSITY OF PENNSYLVANIA · PI GREENBERG, ROGER A · 2013 to 2025
$4.0M
Nanoscience of 'Self' - reductionist approaches to hCD47 inhibition of phagocytesR01HL124106 · NHLBI · UNIVERSITY OF PENNSYLVANIA · PI DISCHER, DENNIS E. · 2014 to 2022
$3.1M
NCI NIH HHS R01 CA138835NCI NIH HHS R01 CA174904NCI NIH HHS U54 CA193417NHLBI NIH HHS R01 HL124106NIGMS NIH HHS R01 GM101149
6 · The paper itself

Abstract

Migration through micron-size constrictions has been seen to rupture the nucleus, release nuclear-localized GFP, and cause localized accumulations of ectopic 53BP1-a DNA repair protein. Here, constricted migration of two human cancer cell types and primary mesenchymal stem cells (MSCs) increases DNA breaks throughout the nucleoplasm as assessed by endogenous damage markers and by electrophoretic "comet" measurements. Migration also causes multiple DNA repair proteins to segregate away from DNA, with cytoplasmic mis-localization sustained for many hours as is relevant to delayed repair. Partial knockdown of repair factors that also regulate chromosome copy numbers is seen to increase DNA breaks in U2OS osteosarcoma cells without affecting migration and with nucleoplasmic patterns of damage similar to constricted migration. Such depletion also causes aberrant levels of DNA. Migration-induced nuclear damage is nonetheless reversible for wild-type and sub-cloned U2OS cells, except for lasting genomic differences between stable clones as revealed by DNA arrays and sequencing. Gains and losses of hundreds of megabases in many chromosomes are typical of the changes and heterogeneity in bone cancer. Phenotypic differences that arise from constricted migration of U2OS clones are further illustrated by a clone with a highly elongated and stable MSC-like shape that depends on microtubule assembly downstream of the transcription factor GATA4. Such changes are consistent with reversion to a more stem-like state upstream of cancerous osteoblastic cells. Migration-induced genomic instability can thus associate with heritable changes.

Indexed as

Cell MovementDNA DamageDNA RepairGenome, HumanBone NeoplasmsCell NucleusGenetic VariationGenomic InstabilityHumansOsteosarcomaTranscription FactorsTumor Cells, CulturedTranscription Factorscancercopy number variationDNA damageDNA repairextracellular matrixlaminamigrationmotilitynuclear enveloperupture

Identifiers

PMID27989676
PMCPMC5262636
OpenAlexW2564267981

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.