ArticleProceedings of the National Academy of Sciences of the United States of America2006
The DDB1-CUL4ADDB2 ubiquitin ligase is deficient in xeroderma pigmentosum group E and targets histone H2A at UV-damaged DNA sites.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 187 papers.
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.
The trial behind it
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
187 citing papers in PubMed, 315 citations in OpenAlex.
- KDM5D expression is lost in cisplatin‑resistant neuroblastoma cells.Oncology reports · 2026Article
- Interaction of CSN4 to DDB1 regulates its stability and function in DNA damage signaling.Cellular and molecular life sciences : CMLS · 2026Article
- XPC-RAD23B enhances UV-DDB binding to DNA to facilitate lesion search in nucleotide excision repair.Nucleic acids research · 2025Article
- Inhibiting neddylation: A new strategy for tumor therapy.Journal of pharmaceutical analysis · 2025Review
- Review
- Sequential post-translational modifications regulate damaged DNA-binding protein DDB2 function.Journal of biochemistry · 2024Article
- An integrated analysis of multiple datasets reveals novel gene signatures in human granulosa cells.Scientific data · 2024Article
- Cullin-RING E3 ubiquitin ligase 4 regulates neurite morphogenesis during neurodevelopment.iScience · 2024Article
- The Cross-Regulation Between Set1, Clr4, and Lsd1/2 in Schizosaccharomyces pombe.PLoS genetics · 2024Article
- Function, mechanism and drug discovery of ubiquitin and ubiquitin-like modification with multiomics profiling for cancer therapy.Acta pharmaceutica Sinica. B · 2023Review
- DDB1 regulates the activation-induced apoptosis of T cells via downregulating the expression of histone methyltransferase SETD7.Medical oncology (Northwood, London, England) · 2023Article
- BAP1 as a guardian of genome stability: implications in human cancer.Experimental & molecular medicine · 2023Review
- Protein post-translational modifications in the regulation of cancer hallmarks.Cancer gene therapy · 2023Review
- Cooperative interaction between AAG and UV-DDB in the removal of modified bases.Nucleic acids research · 2022Article
- BAP1 promotes the repair of UV-induced DNA damage via PARP1-mediated recruitment to damage sites and control of activity and stability.Cell death and differentiation · 2022Article
- A protein with broad functions: damage-specific DNA-binding protein 2.Molecular biology reports · 2022Review
- Review
- Nucleotide excision repair: a versatile and smart toolkit.Acta biochimica et biophysica Sinica · 2022Review
- M6A RNA Methylation Regulates Histone Ubiquitination to Support Cancer Growth and Progression.Cancer research · 2022Article
- Histone deacetylation regulates nucleotide excision repair through an interaction with the XPC protein.iScience · 2022Article
127 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Xeroderma pigmentosum (XP) is a heritable human disorder characterized by defects in nucleotide excision repair (NER) and the development of skin cancer. Cells from XP group E (XP-E) patients have a defect in the UV-damaged DNA-binding protein complex (UV-DDB), involved in the damage recognition step of NER. UV-DDB comprises two subunits, products of the DDB1 and DDB2 genes, respectively. Mutations in the DDB2 gene account for the underlying defect in XP-E. The UV-DDB complex is a component of the newly identified cullin 4A-based ubiquitin E3 ligase, DDB1-CUL4A(DDB2). The E3 ubiquitin ligases recognize specific substrates and mediate their ubiquitination to regulate protein activity or target proteins for degradation by the proteasomal pathway. In this study, we have addressed the role of the UV-DDB-based E3 in NER and sought a physiological substrate. We demonstrate that monoubiquitinated histone H2A in native chromatin coimmunoprecipitates with the endogenous DDB1-CUL4A(DDB2) complex in response to UV irradiation. Further, mutations in DDB2 alter the formation and binding activity of the DDB1-CUL4A(DDB2) ligase, accompanied by impaired monoubiquitination of H2A after UV treatment of XP-E cells, compared with repair-proficient cells. This finding indicates that DDB2, as the substrate receptor of the DDB1-CUL4A-based ligase, specifically targets histone H2A for monoubiquitination in a photolesion-binding-dependent manner. Given that the loss of monoubiquitinated histone H2A at the sites of UV-damaged DNA is associated with decreased global genome repair in XP-E cells, this study suggests that histone modification, mediated by the XPE factor, facilitates the initiation of NER.
Indexed as
Identifiers
What OpenQuestion holds
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.