Evidence map›Paper›PMID 40114375›Full record

ArticleNucleic acids research2025

Homeodomain protein PRRX1 anchors the Ku heterodimers at DNA double-strand breaks to promote nonhomologous end-joining.

Yan Wang, Fuyuan Shen, Chen Zhao, Jiali Li, Wen Wang, Yamu Li, Jia Gan, Haojian Zhang, Xuefeng Chen, Qiang Chen and 3 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Nucleic acids research, 2025. 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

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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.

Yan WangDepartment of Neurosurgery, Medical Research Institute, Zhongnan Hospital of Wuhan University, Wuhan University, Wuhan 430071, China.
Fuyuan ShenDepartment of Neurosurgery, Medical Research Institute, Zhongnan Hospital of Wuhan University, Wuhan University, Wuhan 430071, China.
Chen ZhaoDepartment of Neurosurgery, Medical Research Institute, Zhongnan Hospital of Wuhan University, Wuhan University, Wuhan 430071, China.
Jiali LiDepartment of Neurosurgery, Medical Research Institute, Zhongnan Hospital of Wuhan University, Wuhan University, Wuhan 430071, China.
Wen WangDepartment of Neurosurgery, Medical Research Institute, Zhongnan Hospital of Wuhan University, Wuhan University, Wuhan 430071, China.
Yamu LiThe First Affiliated Hospital of Henan University, Kaifeng 475004, China.
Jia GanDepartment of Neurosurgery, Medical Research Institute, Zhongnan Hospital of Wuhan University, Wuhan University, Wuhan 430071, China.
Haojian ZhangFrontier Science Center of Immunology and Metabolism, Wuhan University, Wuhan 430071, China.
Xuefeng ChenFrontier Science Center of Immunology and Metabolism, Wuhan University, Wuhan 430071, China.ORCID 0000-0002-7990-4111
Qiang ChenFrontier Science Center of Immunology and Metabolism, Wuhan University, Wuhan 430071, China.
Fangyu WangDepartment of Neurosurgery, Medical Research Institute, Zhongnan Hospital of Wuhan University, Wuhan University, Wuhan 430071, China.
Ying LiuDepartment of Neurosurgery, Medical Research Institute, Zhongnan Hospital of Wuhan University, Wuhan University, Wuhan 430071, China.
Yan ZhouDepartment of Neurosurgery, Medical Research Institute, Zhongnan Hospital of Wuhan University, Wuhan University, Wuhan 430071, China.ORCID 0000-0002-2713-4442

Funding

Fundamental Research Funds for the Central Universities 2042022dx0003National Key R&D Program of China 2022YFA0806603National Natural Science Foundation of China 32470776
6 · The paper itself

Abstract

The DNA-dependent protein kinase (DNA-PK) complex plays a critical role in nonhomologous end-joining (NHEJ), a template-independent pathway for repairing DNA double-strand breaks (DSBs). The association of Ku70/80 with DSB ends facilitates the assembly of the DNA-PK holoenzyme. However, key mechanisms underlying the attachment and stabilization of DNA-PK at broken DNA ends remain unclear. Here, we identify PRRX1, a homeodomain-containing protein, as a mediator of chromatin localization and subsequent activation of DNA-PK. PRRX1 oligomerizes to simultaneously bind to double-strand DNA and the SAP (SAF-A/B, Acinus, and PIAS) domain of Ku70, thereby enhancing Ku anchoring at DSBs and stabilizing DNA-PK for efficient NHEJ repair. Reduced expression or pathogenic mutations of PRRX1 are associated with genomic instability and impaired NHEJ repair. Furthermore, a peptide that disrupts PRRX1 oligomerization compromises NHEJ efficiency and reduces cell survival following irradiation. These findings provide new insights into the activation of the NHEJ machinery and offer potential strategies for optimizing cancer therapies.

Indexed as

DNA Breaks, Double-StrandedDNA End-Joining RepairHomeodomain ProteinsKu AutoantigenAnimalsChromatinDNADNA-Activated Protein KinaseGenomic InstabilityHEK293 CellsHumansMutationProtein BindingProtein MultimerizationChromatinDNADNA-Activated Protein KinaseHomeodomain ProteinsKu AutoantigenPRRX1 protein, humanXrcc6 protein, human

Identifiers

PMID40114375
PMCPMC11925728

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