Evidence map›Paper›PMID 42277940›Full record

ArticleGenome biology2026

DNA-contact mutant p53 displaces BRCA2 from chromatin and drives R-loop-associated genome instability.

Fanfan Li, Ke Fang, Shuhan Si, Quanyong Zhang, Menghan Fan, Chenghao Guo, Jie Sun, Zhuoying Xie, Kai Chen, Zhiyong Chen and 3 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Genome biology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing 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

1 citing paper in PubMed.

  1. 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

13 authors.

Fanfan Li *Department of Hematology, Key Laboratory of Developmental Genes and Human Disease, School of Life Science and Technology, Zhongda Hospital, Southeast University, Nanjing, China.
Ke Fang *Department of Hematology, Key Laboratory of Developmental Genes and Human Disease, School of Life Science and Technology, Zhongda Hospital, Southeast University, Nanjing, China.
Shuhan SiDepartment of Hematology, Key Laboratory of Developmental Genes and Human Disease, School of Life Science and Technology, Zhongda Hospital, Southeast University, Nanjing, China.
Quanyong ZhangState Key Laboratory of Primate Biomedical Research, Institute of Primate Translational Medicine, Kunming University of Science and Technology, Kunming, China.
Menghan FanDepartment of Hematology, Key Laboratory of Developmental Genes and Human Disease, School of Life Science and Technology, Zhongda Hospital, Southeast University, Nanjing, China.
Chenghao GuoDepartment of Hematology, Key Laboratory of Developmental Genes and Human Disease, School of Life Science and Technology, Zhongda Hospital, Southeast University, Nanjing, China.
Jie SunState Key Laboratory of Digital Medical Engineering, School of Biological Science and Medical Engineering, Southeast University, Nanjing, China.
Zhuoying XieState Key Laboratory of Digital Medical Engineering, School of Biological Science and Medical Engineering, Southeast University, Nanjing, China.
Kai ChenSouthern Marine Science and Engineering Guangdong Laboratory, Guangzhou, China.
Zhiyong ChenFunctional Neurosurgery, the Affiliated Hospital of Jinan University, Guangzhou, China.
Zheng GeDepartment of Hematology, Key Laboratory of Developmental Genes and Human Disease, School of Life Science and Technology, Zhongda Hospital, Southeast University, Nanjing, China.
Chengqi LinDepartment of Hematology, Key Laboratory of Developmental Genes and Human Disease, School of Life Science and Technology, Zhongda Hospital, Southeast University, Nanjing, China.
Zhuojuan LuoDepartment of Hematology, Key Laboratory of Developmental Genes and Human Disease, School of Life Science and Technology, Zhongda Hospital, Southeast University, Nanjing, China. zjluo@seu.edu.cn.

Funding

Basic Research Program of Jiangsu BK20253017National Natural Science Foundation of China 32370599National Natural Science Foundation of China 32470627National Natural Science Foundation of China 32561160132Shenzhen Science and Technology Program JCYJ20250604125531001ZhiShan Scholar Program of Southeast University 2242022R40063
6 · The paper itself

Abstract

backgroundMutations in the tumor suppressor p53 are among the most frequent events in human cancers. Mutant p53 acquires oncogenic activities beyond the loss of tumor suppressive function. However, how different mutation subtypes differ in their contributions to tumorigenesis remains incompletely understood.

resultsThrough pan-cancer TCGA analysis, we find that patients with p53 DNA contact mutations exhibit worse clinical outcomes than those carrying conformational mutations. Mechanistically, we demonstrate that the DNA contact mutation p53-R273H forms aberrant condensates that sequester BRCA2 and displace it from chromatin, leading to R-loop accumulation and genomic instability. We further identify the DEAD-box helicase DDX3X as a critical factor required for BRCA2-dependent R-loop resolution. Pharmacological inhibition of DDX3X with RK-33 synergizes with the PARP inhibitor Olaparib, enhancing therapeutic efficacy in p53 DNA contact mutant cancer cells.

conclusionsOur study establishes a pathogenic axis through which the clinically aggressive p53 DNA contact mutations drive genomic instability by dislodging BRCA2 from chromatin and disrupting R-loop homeostasis. These findings suggest a potential therapeutic avenue for treating cancers harboring high-risk p53 DNA contact mutations.

Indexed as

BRCA2 ProteinChromatinGenomic InstabilityMutationR-Loop StructuresTumor Suppressor Protein p53Cell Line, TumorDEAD-box RNA HelicasesHumansNeoplasmsPhthalazinesPiperazinesBRCA2 ProteinBRCA2 protein, humanChromatinDDX3X protein, humanDEAD-box RNA HelicasesolaparibPhthalazinesPiperazinesTP53 protein, humanTumor Suppressor Protein p53BRCA2CancerDDX3Xp53 mutantR-loop

Identifiers

PMID42277940
PMCPMC13483591

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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.