ArticleOncogene2014
Coordinated regulation of XPA stability by ATR and HERC2 during nucleotide excision repair.
Article in Oncogene, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers.
What it found
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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.
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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.
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Who cites it
45 citing papers in PubMed, 60 citations in OpenAlex.
- XPA lactylation is required for UV-induced DNA damage repair.Nucleic acids research · 2026Article
- The role of HECT-type E3 ubiquitin ligases in DNA damage response and repair.Cell death discovery · 2025Review
- Targeting the DNA damage response in cancer.MedComm · 2024Review
- ATR kinase supports normal proliferation in the early S phase by preventing replication resource exhaustion.Nature communications · 2023Article
- HERC2 promotes inflammation-driven cancer stemness and immune evasion in hepatocellular carcinoma by activating STAT3 pathway.Journal of experimental & clinical cancer research : CR · 2023Article
- Targeting ATR in Cancer Medicine.Cancer treatment and research · 2023Article
- The XPA Protein-Life under Precise Control.Cells · 2022Review
- HERC2 deficiency activates C-RAF/MKK3/p38 signalling pathway altering the cellular response to oxidative stress.Cellular and molecular life sciences : CMLS · 2022Article
- Nucleotide Excision Repair Pathway Activity Is Inhibited by Airborne Particulate Matter (PMInternational journal of molecular sciences · 2022Article
- XPA is susceptible to proteolytic cleavage by cathepsin L during lysis of quiescent cells.DNA repair · 2022Article
- Beta-Genus Human Papillomavirus 8 E6 Destabilizes the Host Genome by Promoting p300 Degradation.Viruses · 2021Review
- Review
- Circadian Rhythm of NER and ATR Pathways.Biomolecules · 2021Review
- ATR prevents CaFASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2021Article
- Novel loss-of-function mutation inJournal of medical genetics · 2021Article
- Solar ultraviolet-induced DNA damage response: Melanocytes story in transformation to environmental melanomagenesis.Environmental and molecular mutagenesis · 2020Review
- HERC Ubiquitin Ligases in Cancer.Cancers · 2020Review
- Posttranscriptional control of the replication stress response via TTP-mediated Claspin mRNA stabilization.Oncogene · 2020Article
- XPA: DNA Repair Protein of Significant Clinical Importance.International journal of molecular sciences · 2020Review
- Increased levels of XPA might be the basis of cisplatin resistance in germ cell tumours.BMC cancer · 2020Article
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
ATR (ATM and Rad3-related) is an essential regulator of the nucleotide excision repair (NER) mechanism. For NER activation, ATR phosphorylates XPA, the rate-limiting factor in the NER pathway. However, the role of XPA phosphorylation at serine 196 by ATR has been elusive. Here we show that ATR-mediated XPA phosphorylation enhances XPA stability by inhibiting HERC2-mediated ubiquitination and subsequent degradation. We analyzed stabilization of XPA with substitutions of Ser 196 either to aspartate (S196D), a phosphomimetic mutation, or to alanine (S196A), a phosphodeficient mutation. Upon ultraviolet damage, ATR facilitated HERC2 dissociation from the XPA complex to induce XPA stabilization. However, this regulation was abrogated in S196A-complemented XPA-deficient cells due to persistent association of HERC2 with this XPA complex, resulting in enhanced ubiquitination of S196A. Conversely, the S196D substitution showed delayed degradation kinetics compared with the wild-type and less binding with HERC2, resulting in reduced ubiquitination of S196D. We also found that XPA phosphorylation enhanced the chromatin retention of XPA, the interaction with its binding partners following DNA damage. Taken together, our study presents a novel control mechanism in the NER pathway by regulating the steady-state level of XPA through posttranslational modifications by which ATR-mediated phosphorylation induces XPA stabilization by antagonizing HERC2-catalyzed XPA ubiquitination.
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Registered trials
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.