Evidence map›Paper›PMID 39805921›Full record

ArticleNature cell biology2025

Homologous recombination promotes non-immunogenic mitotic cell death upon DNA damage.

Radoslaw Szmyd, Sienna Casolin, Lucy French, Anna G Manjón, Melanie Walter, Léa Cavalli, Christopher B Nelson, Scott G Page, Andrew Dhawan, Eric Hau and 3 more

Abstract read
In one paragraph

Article in Nature cell biology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.

0numbers the graph read from it
0cells of the map it votes in
9citing papers in PubMed
–field-weighted citation impact
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

9 citing papers in PubMed.

  1. Article
  2. Article
  3. Article
  4. Review
  5. DNA-repair-driven cell death compels us to rethink cancer therapies.Nature reviews. Molecular cell biology · 2025
    Article
  6. Article
  7. A concise guide to fluorescent cell cycle reporters for live-cell imaging.Frontiers in cell and developmental biology · 2025
    Review
  8. Mitotic lethality prevents inflammation.Nature cell biology · 2025
    Article
  9. Review
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.

Radoslaw SzmydGenome Integrity Unit, Children's Medical Research Institute, University of Sydney, Westmead, New South Wales, Australia.ORCID 0000-0001-9066-5775
Sienna CasolinGenome Integrity Unit, Children's Medical Research Institute, University of Sydney, Westmead, New South Wales, Australia.ORCID 0000-0003-0357-0909
Lucy FrenchGenome Integrity Unit, Children's Medical Research Institute, University of Sydney, Westmead, New South Wales, Australia.ORCID 0009-0007-5568-6651
Anna G ManjónGenome Integrity Unit, Children's Medical Research Institute, University of Sydney, Westmead, New South Wales, Australia.
Melanie WalterGenome Integrity Unit, Children's Medical Research Institute, University of Sydney, Westmead, New South Wales, Australia.ORCID 0000-0003-3241-522X
Léa CavalliGenome Integrity Unit, Children's Medical Research Institute, University of Sydney, Westmead, New South Wales, Australia.
Christopher B NelsonTelomere Length Regulation Unit, Children's Medical Research Institute, University of Sydney, Westmead, New South Wales, Australia.ORCID 0000-0002-0223-4121
Scott G PageGenome Integrity Unit, Children's Medical Research Institute, University of Sydney, Westmead, New South Wales, Australia.ORCID 0000-0002-4659-5543
Andrew DhawanNeurological Institute, Cleveland Clinic, Cleveland, OH, USA.ORCID 0000-0002-5027-1277
Eric HauRadiation Oncology Network, Western Sydney Local Health District, Sydney, New South Wales, Australia.
Hilda A PickettTelomere Length Regulation Unit, Children's Medical Research Institute, University of Sydney, Westmead, New South Wales, Australia.ORCID 0000-0002-9840-4841
Harriet E GeeGenome Integrity Unit, Children's Medical Research Institute, University of Sydney, Westmead, New South Wales, Australia. harriet.gee@sydney.edu.au.ORCID 0000-0001-7397-8585
Anthony J CesareGenome Integrity Unit, Children's Medical Research Institute, University of Sydney, Westmead, New South Wales, Australia. tcesare@cmri.org.au.ORCID 0000-0002-0864-1254

Funding

Department of Health | National Health and Medical Research Council (NHMRC) 1106241Department of Health | National Health and Medical Research Council (NHMRC) 2004430
6 · The paper itself

Abstract

Double-strand breaks (DSBs) can initiate mitotic catastrophe, a complex oncosuppressive phenomenon characterized by cell death during or after cell division. Here we unveil how cell cycle-regulated DSB repair guides disparate cell death outcomes through single-cell analysis of extended live imaging. Following DSB induction in S or G2, passage of unresolved homologous recombination intermediates into mitosis promotes non-immunogenic intrinsic apoptosis in the immediate attempt at cell division. Conversely, non-homologous end joining, microhomology-mediated end joining and single-strand annealing cooperate to enable damaged G1 cells to complete the first cell cycle with an aberrant cell division at the cost of delayed extrinsic lethality and interferon production. Targeting non-homologous end joining, microhomology-mediated end joining or single-strand annealing promotes mitotic death, while suppressing mitotic death enhances interferon production. Together the data indicate that a temporal repair hierarchy, coupled with cumulative DSB load, serves as a reliable predictor of mitotic catastrophe outcomes following genome damage. In this pathway, homologous recombination suppresses interferon production by promoting mitotic lethality.

Indexed as

ApoptosisDNA Breaks, Double-StrandedDNA DamageHomologous RecombinationMitosisCell DeathDNA End-Joining RepairHeLa CellsHumansRecombinational DNA RepairSingle-Cell Analysis

Identifiers

PMID39805921
PMCPMC11735404

What OpenQuestion holds

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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.