Evidence map›Paper›PMID 41278855›Full record

ArticlebioRxiv : the preprint server for biology2025

APOBEC3A-Induced DNA Damage Drives Polymerase θ Dependency and Synthetic Lethality in Cancer.

Abhishek Bose, Weisi Liu, Paul Yoo, Alina Sami, Michal T Boniecki, Madhura Deshpande, Mohamed Osman, Duy Nguyen, Urko D Castillo, Paraskevi Giannakakou and 9 more

Abstract readPreprint
PubMed Full text at PMC Publisher
In one paragraph

Article in bioRxiv : the preprint server for biology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing 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

0 citing papers in PubMed.

No citing paper in PubMed yet.

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

19 authors.

Abhishek BoseDepartment of Medicine, Weill Cornell Medicine, New York, NY, USA.ORCID 0000-0003-3940-9463
Weisi LiuDepartment of Medicine, Weill Cornell Medicine, New York, NY, USA.
Paul YooDepartment of Medicine, Weill Cornell Medicine, New York, NY, USA.
Alina SamiCollege of Medicine, Biochemistry, Microbiology & Immunology, University of Saskatchewan, Saskatoon, Saskatchewan, Canada.
Michal T BonieckiCollege of Medicine, Biochemistry, Microbiology & Immunology, University of Saskatchewan, Saskatoon, Saskatchewan, Canada.
Madhura DeshpandeThe Ronald O. Perelman and Claudia Cohen Center for Reproductive Medicine, Weill Cornell Medicine, New York, NY, USA.
Mohamed OsmanDepartment of Medicine, Weill Cornell Medicine, New York, NY, USA.
Duy NguyenDepartment of Medicine, Weill Cornell Medicine, New York, NY, USA.
Urko D CastilloDepartment of Medicine, Weill Cornell Medicine, New York, NY, USA.
Paraskevi GiannakakouDepartment of Medicine, Weill Cornell Medicine, New York, NY, USA.ORCID 0000-0001-7378-262X
Bhavneet BhinderEnglander Institute for Precision Medicine, Weill Cornell Medicine, New York, NY, USA.
William HooperNew York Genome Center, New York, NY, USA.
Olivier ElementoEnglander Institute for Precision Medicine, Weill Cornell Medicine, New York, NY, USA.
Nicolas RobineNew York Genome Center, New York, NY, USA.ORCID 0000-0001-5698-8183
Milaid Granadillo RodriguezCollege of Medicine, Biochemistry, Microbiology & Immunology, University of Saskatchewan, Saskatoon, Saskatchewan, Canada.
Jeannine GerhardtThe Ronald O. Perelman and Claudia Cohen Center for Reproductive Medicine, Weill Cornell Medicine, New York, NY, USA.
Kent W MouwBrigham & Women's Hospital, Dana Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.
Linda ChelicoCollege of Medicine, Biochemistry, Microbiology & Immunology, University of Saskatchewan, Saskatoon, Saskatchewan, Canada.
Bishoy M FaltasDepartment of Medicine, Weill Cornell Medicine, New York, NY, USA.ORCID 0000-0002-6432-1693

Funding

Targeting APOBEC3A-induced genetic heterogeneity and drug resistance in bladder cancerR37CA279737 · NCI · WEILL MEDICAL COLL OF CORNELL UNIV · PI Bishoy Morris Faltas · 2023 to 2026
$2.0M
NCI NIH HHS R37 CA279737
6 · The paper itself

Abstract

APOBEC3 cytidine deaminases drive cancer evolution. There is an unmet need to target cancer cells with APOBEC3 activity. Here, we identify error-prone theta-mediated end joining (TMEJ) as the main pathway for repairing APOBEC3-induced double-strand breaks (DSBs). Using fluorescent DSB repair reporters and a novel biochemical assay, we demonstrate that APOBEC3A competes with replication protein A (RPA) for single-stranded DNA overhangs, exposing microhomologous sequences to shift DSB repair towards error-prone TMEJ. Genomic analysis of clinical tumor samples confirmed the cooccurrence and proximity between APOBEC3-induced mutational footprints, microhomology-mediated deletions (MMDs), and TMEJ-associated chromosomal instability signatures. Crucially, inhibition of DNA polymerase theta (Polθ) synergizes with APOBEC3A-induced DSBs to induce synthetic lethality

Identifiers

PMID41278855
PMCPMC12633405

What OpenQuestion holds

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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.