ArticlePLoS genetics2011
Genomic instability, defective spermatogenesis, immunodeficiency, and cancer in a mouse model of the RIDDLE syndrome.
Article in PLoS genetics, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 52 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
52 citing papers in PubMed, 80 citations in OpenAlex.
- Driver or passenger? A new assessment of genes in the schizophrenia-associated 3q29 deletion locus for contribution to neurodevelopmental disorders.Journal of neurodevelopmental disorders · 2026Review
- Mechanisms of RNF168 nucleosome recognition and ubiquitylation.Molecular cell · 2024Article
- The ubiquitin codes in cellular stress responses.Protein & cell · 2024Review
- Review
- Review
- Causal and Candidate Gene Variants in a Large Cohort of Women With Primary Ovarian Insufficiency.The Journal of clinical endocrinology and metabolism · 2022Observational
- Review
- RNF168 regulates R-loop resolution and genomic stability in BRCA1/2-deficient tumors.The Journal of clinical investigation · 2021Article
- UBC13-Mediated Ubiquitin Signaling Promotes Removal of Blocking Adducts from DNA Double-Strand Breaks.iScience · 2020Article
- Human papillomavirus E7 oncoprotein targets RNF168 to hijack the host DNA damage response.Proceedings of the National Academy of Sciences of the United States of America · 2019Article
- BRCA1 Haploinsufficiency Is Masked by RNF168-Mediated Chromatin Ubiquitylation.Molecular cell · 2019Article
- The mTOR-S6K pathway links growth signalling to DNA damage response by targeting RNF168.Nature cell biology · 2018Article
- Review
- Generating and repairing genetically programmed DNA breaks during immunoglobulin class switch recombination.F1000Research · 2018Review
- Genomic analysis of exceptional responders to radiotherapy reveals somatic mutations in ATM.Oncotarget · 2017Article
- An E2-guided E3 Screen Identifies the RNF17-UBE2U Pair as Regulator of the Radiosensitivity, Immunodeficiency, Dysmorphic Features, and Learning Difficulties (RIDDLE) Syndrome Protein RNF168.The Journal of biological chemistry · 2017Article
- Clinical and Biological Manifestation of RNF168 Deficiency in Two Polish Siblings.Frontiers in immunology · 2017Article
- Novel Combined Immune Deficiency and Radiation Sensitivity Blended Phenotype in an Adult with Biallelic Variations inFrontiers in immunology · 2017Article
- A role for the p53 tumour suppressor in regulating the balance between homologous recombination and non-homologous end joining.Open biology · 2016Article
- RNF168 and USP10 regulate topoisomerase IIα function via opposing effects on its ubiquitylation.Nature communications · 2016Article
Corrections and comments
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Authors and funding
12 authors at 7 institutions in 3 countries.
Funding
Abstract
Eukaryotic cells have evolved to use complex pathways for DNA damage signaling and repair to maintain genomic integrity. RNF168 is a novel E3 ligase that functions downstream of ATM,γ-H2A.X, MDC1, and RNF8. It has been shown to ubiquitylate histone H2A and to facilitate the recruitment of other DNA damage response proteins, including 53BP1, to sites of DNA break. In addition, RNF168 mutations have been causally linked to the human RIDDLE syndrome. In this study, we report that Rnf168(-/-) mice are immunodeficient and exhibit increased radiosensitivity. Rnf168(-/-) males suffer from impaired spermatogenesis in an age-dependent manner. Interestingly, in contrast to H2a.x(-/-), Mdc1(-/-), and Rnf8(-/-) cells, transient recruitment of 53bp1 to DNA double-strand breaks was abolished in Rnf168(-/-) cells. Remarkably, similar to 53bp1 inactivation, but different from H2a.x deficiency, inactivation of Rnf168 impairs long-range V(D)J recombination in thymocytes and results in long insertions at the class-switch junctions of B-cells. Loss of Rnf168 increases genomic instability and synergizes with p53 inactivation in promoting tumorigenesis. Our data reveal the important physiological functions of Rnf168 and support its role in both γ-H2a.x-Mdc1-Rnf8-dependent and -independent signaling pathways of DNA double-strand breaks. These results highlight a central role for RNF168 in the hierarchical network of DNA break signaling that maintains genomic integrity and suppresses cancer development in mammals.
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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.