Evidence map›Paper›PMID 41120267›Full record

ArticleCell death & disease2025

Phosphorylation of RNF213 by ATM-mediated ubiquitination of RPA1 regulates homologous recombination repair and chemosensitivity.

Dingwen Hu, Wenli Wu, Chenhao Wu, Jun Li, Bin Ruan, Heng Cheng, Yanxia Jiang, Yili Wang, Zhiwang Song

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PubMed Full text at PMC Publisher
In one paragraph

Article in Cell death & disease, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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1 · What the graph read from it

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2 · The registry

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3 · Its place in the literature

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4 · The record

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5 · Who and what money

Authors and funding

9 authors.

Dingwen HuDepartment of Medical Care Center, Hainan Women and Children's Medical Center, Haikou, Hainan, China.
Wenli WuDepartment of Medical Care Center, Hainan Women and Children's Medical Center, Haikou, Hainan, China.
Chenhao WuDepartment of Medical Care Center, Hainan Women and Children's Medical Center, Haikou, Hainan, China.
Jun LiDepartment of Medical Care Center, Hainan Women and Children's Medical Center, Haikou, Hainan, China.
Bin RuanDepartment of Medical Care Center, Hainan Women and Children's Medical Center, Haikou, Hainan, China.
Heng ChengDepartment of Medical Care Center, Hainan Women and Children's Medical Center, Haikou, Hainan, China.
Yanxia JiangDepartment of Oncology, Mayo Clinic, Rochester, MN, USA. jiang.yanxia@mayo.edu.
Yili WangPrevention and Cure Center of Breast Disease, The Third Hospital of Nanchang City, Nanchang, Jiangxi, China. yiliwang2008@hotmail.com.
Zhiwang SongDepartment of Medical Care Center, Hainan Women and Children's Medical Center, Haikou, Hainan, China. song.zhiwang@mayo.edu.ORCID http://orcid.org/0000-0001-9342-9612

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Replication protein A1 (RPA1) is a crucial regulator of homologous recombination (HR) repair and DNA end resection. Studies have demonstrated that the expression and activity of RPA1 are regulated through posttranslational modifications. However, the exact molecular mechanism through which RPA1 activity is regulated remains unclear. Here, we discovered that RNF213 interacts directly with and ubiquitinates RPA1, thereby inhibiting HR repair and DNA end resection. Furthermore, RNF213 is phosphorylated by ATM at Ser217 following DNA damage, which increases the catalytic activity of RNF213. In addition, RNF213 overexpression sensitizes triple-negative breast cancer (TNBC) cells to PARP inhibitor (PARPi) treatment in an RPA1-dependent manner both in vitro and in vivo. Taken together, our findings reveal that RNF213 modulates the response of TNBC cells to PARPi treatment by regulating the ubiquitination of RPA1 and inhibiting HR repair.

Indexed as

Ataxia Telangiectasia Mutated ProteinsRecombinational DNA RepairReplication Protein ATriple Negative Breast NeoplasmsUbiquitin-Protein LigasesAnimalsCell Line, TumorDNA DamageFemaleHEK293 CellsHumansMiceMice, NudePhosphorylationPoly(ADP-ribose) Polymerase InhibitorsUbiquitinationAtaxia Telangiectasia Mutated ProteinsATM protein, humanPoly(ADP-ribose) Polymerase InhibitorsReplication Protein ARPA1 protein, humanUbiquitin-Protein Ligases

Identifiers

PMID41120267
PMCPMC12540995

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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.