ArticleCell death & disease2015
PHRF1 promotes genome integrity by modulating non-homologous end-joining.
Article in Cell death & disease, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 39 citations in OpenAlex.
- XPC Deficiency Activate Cisplatin-Mediated Autophagy in Bladder Cancer by Limiting Novel PHRF1-Mediated Ubiquitination of the p53 Protein.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Emerging role of SETD2 in the development and function of immune cells.Genes & diseases · 2025Review
- Histone H3 N-terminal recognition by the PHD finger of PHRF1 is required for proper DNA damage response.Nucleic acids research · 2025Article
- Mono-ubiquitination of TopBP1 by PHRF1 enhances ATR activation and genomic stability.Nucleic acids research · 2025Article
- Phosphorylation of 'SDT-like' motifs in ATRX mediates its interaction with the MRN complex and is important for ALT pathway suppression.Open biology · 2024Article
- From discovery to application: merging modern omics with traditional hypothesis-driven approaches in muscle myopathy studies.Frontiers in physiology · 2024Article
- Comparative Study of Hydroxytyrosol Acetate and Hydroxytyrosol in Activating Phase II Enzymes.Antioxidants (Basel, Switzerland) · 2023Article
- Targeted Profiling of Epitranscriptomic Reader, Writer, and Eraser Proteins Regulated by H3K36me3.Analytical chemistry · 2023Article
- LncRNA HOTAIRM1 functions in DNA double-strand break repair via its association with DNA repair and mRNA surveillance factors.Nucleic acids research · 2023Article
- Modeling of horizontal pleiotropy identifies possible causal gene expression in systemic lupus erythematosus.Frontiers in lupus · 2023Article
- Histone methyltransferase SETD2: An epigenetic driver in clear cell renal cell carcinoma.Frontiers in oncology · 2023Review
- Article
- SETD2: from chromatin modifier to multipronged regulator of the genome and beyond.Cellular and molecular life sciences : CMLS · 2022Review
- Enzymatic Characterization of In Vitro Activity of RNA Methyltransferase PCIF1 on DNA.Biochemistry · 2022Article
- Review
- Chromatin Regulation through Ubiquitin and Ubiquitin-like Histone Modifications.Trends in biochemical sciences · 2021Review
- An important role of PHRF1 in dendritic architecture and memory formation by modulating TGF-β signaling.Scientific reports · 2020Article
- JMJD6 participates in the maintenance of ribosomal DNA integrity in response to DNA damage.PLoS genetics · 2020Article
- Loss of H3K36 Methyltransferase SETD2 Impairs V(D)J Recombination during Lymphoid Development.iScience · 2020Article
- H3K36me3, message from chromatin to DNA damage repair.Cell & bioscience · 2020Review
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Methylated histone readers are critical for chromatin dynamics, transcription, and DNA repair. Human PHRF1 contains a plant homeodomain (PHD) that recognizes methylated histones and a RING domain, which ubiquitinates substrates. A recent study reveals that PHRF1 is a tumor suppressor that promotes TGF-β cytostatic signaling through TGIF ubiquitination. Also, PHRF1 is a putative phosphorylation substrate of ataxia telangiectasia-mutated/ataxia telangiectasia and Rad3-related kinases; however, the role of PHRF1 in DNA damage response is unclear. Here we report a novel function of PHRF1 in modulating non-homologous end-joining (NHEJ). PHRF1 quickly localizes to DNA damage lesions upon genotoxic insults. Ablation of PHRF1 decreases the efficiency of plasmid-based end-joining, whereas PHRF1 overexpression leads to an elevated NHEJ in H1299 reporter cells. Immunoprecipitation and peptide pull-down assays verify that PHRF1 constitutively binds to di- and trimethylated histone H3 lysine 36 (H3K36) (H3K36me2 and H3K36me3) via its PHD domain. Substitution of S915DT917E to ADAE in PHRF1 decreases its affinity for NBS1. Both PHD domain and SDTE motif are required for its NHEJ-promoting activity. Furthermore, PHRF1 mediates PARP1 polyubiquitination for proteasomal degradation. These results suggest that PHRF1 may combine with H3K36 methylation and NBS1 to promote NHEJ and stabilize genomic integrity upon DNA damage insults.
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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.