ArticleThe Journal of clinical investigation2015
RNF4-mediated polyubiquitination regulates the Fanconi anemia/BRCA pathway.
Article in The Journal of clinical investigation, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 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
30 citing papers in PubMed, 40 citations in OpenAlex.
- The role of SUMOylation in biomolecular condensate dynamics and protein localization.Cell insight · 2024Review
- Deciphering the role of post-translational modifications in fanconi anemia proteins and their influence on tumorigenesis.Cancer gene therapy · 2024Review
- SUMO and the DNA damage response.Biochemical Society transactions · 2024Review
- RNF4 sustains Myc-driven tumorigenesis by facilitating DNA replication.The Journal of clinical investigation · 2024Article
- Review
- Fanconi anemia associated protein 20 (FAAP20) plays an essential role in homology-directed repair of DNA double-strand breaks.Communications biology · 2023Article
- SUMO-Targeted Ubiquitin Ligases and Their Functions in Maintaining Genome Stability.International journal of molecular sciences · 2021Review
- RNF4 Regulates the BLM Helicase in Recovery From Replication Fork Collapse.Frontiers in genetics · 2021Article
- Inactivation of ribosomal protein S27-like impairs DNA interstrand cross-link repair by destabilization of FANCD2 and FANCI.Cell death & disease · 2020Article
- Acetylation modulates the Fanconi anemia pathway by protecting FAAP20 from ubiquitin-mediated proteasomal degradation.The Journal of biological chemistry · 2020Article
- Fanconi anemia and the underlying causes of genomic instability.Environmental and molecular mutagenesis · 2020Review
- Structural basis of the fanconi anemia-associated mutations within the FANCA and FANCG complex.Nucleic acids research · 2020Article
- Molecular Mechanisms of Arsenic-Induced Disruption of DNA Repair.Chemical research in toxicology · 2020Review
- Fanconi Anemia DNA Repair Pathway as a New Mechanism to Exploit Cancer Drug Resistance.Mini reviews in medicinal chemistry · 2020Review
- Proteolytic control of genome integrity at the replication fork.DNA repair · 2019Review
- The SUMO Pathway in Hematomalignancies and Their Response to Therapies.International journal of molecular sciences · 2019Review
- Prolyl isomerization of FAAP20 catalyzed by PIN1 regulates the Fanconi anemia pathway.PLoS genetics · 2019Article
- SUMO Chains Rule on Chromatin Occupancy.Frontiers in cell and developmental biology · 2019Review
- Fanconi anaemia and cancer: an intricate relationship.Nature reviews. Cancer · 2018Review
- The Biology of SUMO-Targeted Ubiquitin Ligases in Drosophila Development, Immunity, and Cancer.Journal of developmental biology · 2018Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 4 institutions in 2 countries.
Funding
Abstract
The Fanconi anemia/BRCA (FA/BRCA) pathway is a DNA repair pathway that is required for excision of DNA interstrand cross-links. The 17 known FA proteins, along with several FA-associated proteins (FAAPs), cooperate in this pathway to detect, unhook, and excise DNA cross-links and to subsequently repair the double-strand breaks generated in the process. In the current study, we identified a patient with FA with a point mutation in FANCA, which encodes a mutant FANCA protein (FANCAI939S). FANCAI939S failed to bind to the FAAP20 subunit of the FA core complex, leading to decreased stability. Loss of FAAP20 binding exposed a SUMOylation site on FANCA at amino acid residue K921, resulting in E2 SUMO-conjugating enzyme UBC9-mediated SUMOylation, RING finger protein 4-mediated (RNF4-mediated) polyubiquitination, and proteasome-mediated degradation of FANCA. Mutation of the SUMOylation site of FANCA rescued the expression of the mutant protein. Wild-type FANCA was also subject to SUMOylation, RNF4-mediated polyubiquitination, and degradation, suggesting that regulated release of FAAP20 from FANCA is a critical step in the normal FA pathway. Consistent with this model, cells lacking RNF4 exhibited interstrand cross-linker hypersensitivity, and the gene encoding RNF4 was epistatic with the other genes encoding members of the FA/BRCA pathway. Together, the results from our study underscore the importance of analyzing unique patient-derived mutations for dissecting complex DNA repair processes.
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.