ArticleOncogene2022
DNA damage-induced translocation of mitochondrial factor HIGD1A into the nucleus regulates homologous recombination and radio/chemo-sensitivity.
Article in Oncogene, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 31 citations in OpenAlex.
- NUP93 facilitates the nuclear import of SOX2 to activate G3BP1 transcription and impairs gemcitabine response in pancreatic cancer.Cell death & disease · 2026Article
- Affinity-Based Protein Profiling Revealed that HIGD1A is a Direct Target Protein of Aristolochic Acids.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- SARS-CoV-2 enhances complement-mediated endothelial injury via the suppression of membrane complement regulatory proteins.Emerging microbes & infections · 2025Article
- Phosphorylation of RNF213 by ATM-mediated ubiquitination of RPA1 regulates homologous recombination repair and chemosensitivity.Cell death & disease · 2025Article
- HIGD1A Alleviates Oxidative Stress Related Ovarian Hypofunction by Enhancing Granulosa Cell Functions via NF-κB/SOD2 Signaling Pathway.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Molecular function validation and prognostic value analysis of the cuproptosis-related gene ferredoxin 1 in papillary thyroid carcinoma.Scientific reports · 2025Article
- ZNF451 collaborates with RNF8 to regulate RNF168 localization and amplify ubiquitination signaling to promote DNA damage repair and regulate radiosensitivity.Cell death and differentiation · 2025Article
- Phospho-TRIM21 orchestrates RPA2 ubiquitination switch to promote homologous recombination and tumor radio/chemo-resistance.Oncogene · 2025Article
- CDC20 Holds Novel Regulation Mechanism in RPA1 during Different Stages of DNA Damage to Induce Radio-Chemoresistance.International journal of molecular sciences · 2024Article
- Procyanidin C1 inhibits tumor growth and metastasis in colon cancer via modulating miR-501-3p/HIGD1A axis.Journal of advanced research · 2024Article
- Elevated expression of HIGD1A drives hepatocellular carcinoma progression by regulating polyamine metabolism through c-Myc-ODC1 nexus.Cancer & metabolism · 2024Article
- Mitochondrial Factors in the Cell Nucleus.International journal of molecular sciences · 2023Review
- Targeting phosphomevalonate kinase enhances radiosensitivity via ubiquitination of the replication protein A1 in lung cancer cells.Cancer science · 2023Article
- Enhancer-driven transcription of MCM8 by E2F4 promotes ATR pathway activation and glioma stem cell characteristics.Hereditas · 2023Article
- Delivery of miR-3529-3p using MnOThoracic cancer · 2023Article
- Protein disulfide isomerase blocks the interaction of LC3II-PHB2 and promotes mTOR signaling to regulate autophagy and radio/chemo-sensitivity.Cell death & disease · 2022Article
- Replicative Stress Coincides with Impaired Nuclear DNA Damage Response in COX4-1 Deficiency.International journal of molecular sciences · 2022Article
Corrections and comments
- Erratum issued
Authors and funding
10 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
HIGD1A is an important mitochondrial protein recently shown to have a novel nuclear localization under severe stress. However, whether this protein is also associated with the DNA damage response has rarely been studied. Here, we reported that DSBs-induced the translocation of mitochondrial HIGD1A to the nucleus is dependent on nuclear pore complex (NPCs), which finally promotes HR and radio/chemo-resistance. Importantly, NUP93 and HIGD1A physically interact and the interaction domain with NUP93 is located at residues 46-60 of HIGD1A. Chromatin-enriched HIGD1A can then directly interact with RPA. During the early stages of HR, HIGD1A promotes the loading of RPA to DSBs and activates the DNA damage-dependent chromatin association of RAD9-RAD1-HUS1 complex (9-1-1), which stimulates the ATR-Chk1-dependent G2/M DNA damage checkpoint. After facilitating RPA-ssDNA binding, HIGD1A in turn inhibits abnormal persistence of RPA1 foci by promoting ubiquitination of RPA1 and inducing its eventual proteasomal degradation. In addition, we have identified clinical drug Preveon associated with the HIGD1A-NUP93 interaction domain using a virtual screening approach. This compound directly interacted with HIGD1A, which was verified by NMR, and then inhibited HIGD1A translocation. Collectively, we demonstrate a novel role for HIGD1A in DSBs and provide rationale for using HIGD1A inhibitors as cancer therapeutics.
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