Affinage

RNF8

E3 ubiquitin-protein ligase RNF8 · UniProt O76064

Length
485 aa
Mass
55.5 kDa
Annotated
2026-06-10
100 papers in source corpus 50 papers cited in narrative 50 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 6/7 claims corpus-supported (86%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

RNF8 is an FHA-RING E3 ubiquitin ligase that nucleates the ubiquitin-dependent signaling cascade at DNA double-strand breaks (DSBs), translating ATM-driven phosphorylation into chromatin ubiquitination that governs repair-factor assembly (PMID:18001824, PMID:18006705). Recruited through phospho-dependent docking of its FHA domain onto ATM-phosphorylated MDC1, RNF8 ubiquitylates histones H2A/H2AX, and its catalytic output is dictated by the E2 it partners: with UBC13 it builds K63-linked chains that recruit 53BP1 and the RAP80-BRCA1 (BRCA1-A) complex (PMID:18006705, PMID:18077395); with UBCH8 it builds K48-linked chains targeting factors such as KU80 for turnover during NHEJ (PMID:22266820, PMID:21911360); and with Ube2S it builds K11-linked chains that enforce DNA damage-induced transcriptional silencing (PMID:28525740). A structurally defined allosteric mechanism by which RNF8 positions Ubc13~ubiquitin underlies its K63 chain-stimulating activity and is required for downstream 53BP1/BRCA1 recruitment (PMID:26903517). RNF8 also possesses a non-catalytic FHA-dependent function, recruiting the CHD4/NuRD remodeler to decondense chromatin and license efficient RNF168 and BRCA1 assembly (PMID:22531782). RNF8-generated ubiquitin marks are read by the L3MBTL2 substrate that bridges RNF8 to RNF168 (PMID:29581593) and by FAAP20 to engage the Fanconi anemia pathway at interstrand crosslinks (PMID:22705371), while opposing DUB activities (BRCC36) and the p97-ATX3 extraction machinery tune RNF8 levels on chromatin to balance repair pathway choice (PMID:19202061, PMID:31613024). Beyond canonical repair, RNF8 drives a trans-histone modification cascade essential for global nucleosome removal and sex-chromosome escape-gene activation during spermatogenesis (PMID:20153262, PMID:23249736) and is required for immunoglobulin class switch recombination (PMID:20385750). It additionally stabilizes telomere-associated proteins TPP1 and tankyrase 1 via K63 ubiquitination (PMID:22101936, PMID:27993934), ubiquitylates substrates to terminate ATR-CHK1 checkpoint signaling (NONO) and to promote R-loop resolution (XRN2) (PMID:30445466, PMID:37697435), and acts in the neuronal cytoplasm with UBC13 to suppress synapse differentiation (PMID:29097665).

Mechanistic history

Synthesis pass · year-by-year structured walk · 24 steps
  1. 2007 High

    Established the founding mechanism: how DSB-flanking chromatin recruits repair effectors, by showing RNF8 reads ATM-phosphorylated MDC1 through its FHA domain and ubiquitylates H2A/H2AX to retain 53BP1 and BRCA1.

    Evidence RNF8 knockdown, FHA/RING domain mutants, and ubiquitylation/foci assays in human cells, replicated across three simultaneous studies

    PMID:18001824 PMID:18001825 PMID:18006705

    Open questions at the time
    • Did not resolve which ubiquitin linkage type drives each downstream branch
    • Direct histone ubiquitination sites not yet mapped
  2. 2007 High

    Provided the structural and physiological basis for phospho-dependent recruitment, solving the FHA domain at 1.35 Å and linking RNF8 loss to a defective G2/M checkpoint and IR sensitivity.

    Evidence X-ray crystallography plus RNF8 depletion and checkpoint/IR sensitivity assays

    PMID:18001825

    Open questions at the time
    • Structure of the catalytic RING~E2 complex not determined here
    • Phosphopeptide specificity beyond MDC1 not defined
  3. 2007 High

    Connected RNF8-generated K63 chains to a specific reader complex, showing RAP80 UIM domains bind these chains to assemble the BRCA1-A complex.

    Evidence siRNA knockdown, domain mapping, and ubiquitin-binding assays

    PMID:18077395

    Open questions at the time
    • Whether RAP80 reads chains on histones or other substrates not resolved
    • Stoichiometry of complex assembly unaddressed
  4. 2006 Medium

    Defined RNF8's basic enzymology, showing RING-dependent recruitment of UBC13 and in vitro capacity for both K48 and K63 chains.

    Evidence Yeast two-hybrid, in vitro ubiquitination, and nuclear co-localization (single lab)

    PMID:16215985

    Open questions at the time
    • Physiological substrate not identified in vitro
    • Chain-type selection rules not yet established
  5. 2011 High

    Resolved how RNF8 selects chain topology, showing a single RING mutation (I405A) uncouples UBCH8/K48 from UBC13/K63 activity.

    Evidence Separation-of-function RING mutant with in vitro reconstitution and cellular validation

    PMID:21911360

    Open questions at the time
    • Substrate determinants of each linkage type not fully mapped
    • K11/Ube2S branch not addressed here
  6. 2012 High

    Distinguished RNF8's degradative role from signaling, showing it primarily builds K48 chains that limit KU80 abundance to permit NHEJ, in contrast to RNF168's K63 output.

    Evidence Linkage-specific antibodies, K48/K63 ubiquitin mutants, knockdown, and NHEJ assays

    PMID:22266820

    Open questions at the time
    • Direct demonstration of KU80 as a direct K48 substrate limited
    • Quantitative balance between K48 and K63 outputs unresolved
  7. 2012 High

    Uncovered a catalysis-independent function, showing RNF8's FHA domain recruits CHD4/NuRD to decondense chromatin and enable efficient RNF168/BRCA1 assembly.

    Evidence RING and FHA separation-of-function mutants, CHD4 depletion, chromatin decondensation assays

    PMID:22531782

    Open questions at the time
    • Molecular basis of the non-canonical FHA-CHD4 interaction not structurally defined
    • How remodeling feeds back on ubiquitin conjugation not quantified
  8. 2012 High

    Expanded the substrate repertoire to chromatin modifiers, showing RNF8 ubiquitylates KDM4A/JMJD2A and Nbs1 to license 53BP1 access and stabilize Nbs1 at breaks.

    Evidence In vitro ubiquitination, proteasome inhibition, epistasis rescue, and HR reporter assays

    PMID:22373579 PMID:23115235

    Open questions at the time
    • Relative contribution of each substrate to repair outcome not weighted
    • Ubiquitination sites on Nbs1 not all mapped
  9. 2012 High

    Defined upstream control of RNF8 recruitment via SUMO, showing PIAS4-SUMOylated HERC2 binds and stabilizes the RNF8-Ubc13 complex through a ZZ SUMO-binding module.

    Evidence SUMO co-IP, PIAS4 knockdown, ZZ zinc-finger mutants, immunofluorescence

    PMID:22508508

    Open questions at the time
    • Direct contribution of HERC2 to chain synthesis kinetics not measured
    • T4827 phosphorylation kinase not identified here
  10. 2009 High

    Established opposing enzymatic control at breaks and broadened RNF8 to other lesions, showing BRCC36 DUB counters RNF8-Ubc13 ubiquitin levels and that RNF8 acts at ATR-dependent UV/NER intermediates.

    Evidence RNF8/BRCC36 knockdown, DUB-inactive mutants, UV survival, and cell-cycle analysis

    PMID:19202061 PMID:19797077

    Open questions at the time
    • Steady-state set-point regulation between writer and eraser not quantitatively modeled
    • MDC1-dependence at UV lesions versus DSBs not fully separated
  11. 2010 High

    Demonstrated RNF8's in vivo physiological roles beyond repair foci, showing knockout mice are defective in spermatogenic nucleosome removal and class switch recombination.

    Evidence RNF8 knockout mouse models, histone modification analysis, CSR and 53BP1 foci assays

    PMID:20153262 PMID:20385750

    Open questions at the time
    • Partial 53BP1 recruitment indicates RNF8-independent routes that were not defined
    • Direct chromatin substrates driving nucleosome removal not all identified
  12. 2010 High

    Revealed viral subversion of RNF8, showing HSV-1 ICP0 degrades RNF8 via CK1-phosphorylated T67 phospho-mimicry of the FHA-binding motif to enhance viral fitness.

    Evidence ICP0 expression, phospho-mimicry mutants, CK1 kinase assay, viral replication assays

    PMID:20075863 PMID:22405594

    Open questions at the time
    • Whether cellular phospho-ligands compete with ICP0 in vivo not measured
    • Generality of FHA hijacking by other pathogens unexplored
  13. 2011 High

    Linked RNF8 to telomere biology, showing it ubiquitylates H2A at uncapped telomeres to drive NHEJ fusions and stabilizes TPP1 via K63 chains at K233.

    Evidence Knockdown/knockout, telomere fusion and length assays, in vitro ubiquitination with site mutant

    PMID:21857671 PMID:22101936

    Open questions at the time
    • Cell-cycle control of telomeric versus DSB RNF8 activity not delineated
    • How TPP1 ubiquitination is read to confer stability not defined
  14. 2011 High

    Placed RNF8 in a histone-modification network controlling ATM activation, showing it acts synergistically with Chfr through MRG15-dependent acetyltransferases on H4K16, with double-knockout mice developing lymphomas.

    Evidence Double-knockout mouse model, ATM kinase assay, acetyltransferase complex co-IP

    PMID:21706008

    Open questions at the time
    • Direct substrate bridging RNF8 ubiquitination to H4K16ac not identified
    • Mechanism of ATM feedback amplification not resolved
  15. 2012 High

    Extended RNF8 signaling to crosslink repair, showing RNF8-UBC13 ubiquitin products are read by FAAP20 to engage the FA core complex and FANCD2 monoubiquitination at ICLs.

    Evidence Ubiquitin-binding assays, RNF8/FAAP20 depletion, FANCD2 monoubiquitination assays

    PMID:22705371

    Open questions at the time
    • The chromatin substrate bearing the FAAP20-read mark not defined
    • Crosstalk with the K48 degradative branch at ICLs not examined
  16. 2012 High

    Detailed sex-chromosome epigenetic programming, showing RNF8-dependent H2A ubiquitination establishes active marks (H3K4me2/me3, crotonylation, H2AFZ) enabling escape-gene activation in spermatids.

    Evidence RNF8 knockout mice with ChIP-seq, RNA-seq, immunofluorescence

    PMID:23249736

    Open questions at the time
    • The reader machinery translating ubiquitin to active marks not identified
    • Direct versus indirect effects on each modification not separated
  17. 2013 High

    Identified a demethylation-based feedback enhancing RNF8 recruitment, showing RNF8 stabilizes JMJD1C, which demethylates MDC1-K45 to strengthen MDC1-RNF8 binding and branch-specific RAP80-BRCA1 recruitment.

    Evidence Co-IP, JMJD1C depletion, methyl-lysine mass spectrometry, immunofluorescence

    PMID:24240613

    Open questions at the time
    • Why this loop favors BRCA1 over 53BP1 not mechanistically resolved
    • In vivo relevance of MDC1-K45 methylation not tested
  18. 2016 High

    Provided the allosteric basis for chain synthesis, showing by crystallography/SAXS that RNF8 reorients Ubc13~ubiquitin to stimulate K63 chains, an activity essential for 53BP1/BRCA1 recruitment.

    Evidence X-ray crystallography, SAXS, structure-guided separation-of-function mutants with cellular validation

    PMID:26903517

    Open questions at the time
    • Structural basis of K48/K11 chain assembly with other E2s not determined
    • Dynamics of E2 exchange on RNF8 not captured
  19. 2017 High

    Established a distinct K11 ubiquitin output with a dedicated function, showing RNF8-Ube2S assembles K11 chains on damaged chromatin that enforce transcriptional silencing.

    Evidence K11-linkage-specific antibodies, Ube2S/RNF8 knockdown, transcriptional silencing assays

    PMID:28525740

    Open questions at the time
    • The reader of K11 chains mediating silencing not identified
    • Substrate specificity of the Ube2S branch not mapped
  20. 2018 High

    Resolved the long-standing RNF8-to-RNF168 hand-off, identifying L3MBTL2 as the ubiquitylated substrate that bridges the two ligases.

    Evidence siRNA knockdown, co-IP, ubiquitylation assays, epistasis, immunofluorescence

    PMID:29581593

    Open questions at the time
    • Reader of ubiquitylated L3MBTL2 recruiting RNF168 not fully defined
    • Whether other parallel bridges exist not excluded
  21. 2021 Medium

    Identified additional chromatin substrates fine-tuning the cascade, showing RNF8 ubiquitylates KMT5A to drive H4K20me1 and supports RNF168 H2A ubiquitination, and removes RecQL4 from breaks to regulate end resection.

    Evidence In vitro ubiquitination, site-directed mutants, ChIP, laser microirradiation, HR assays

    PMID:33674555 PMID:33710666

    Open questions at the time
    • Single-lab findings without reciprocal validation
    • Quantitative contribution of each substrate to pathway choice unclear
  22. 2019 High

    Established negative-feedback and homeostatic control, showing RNF8 ubiquitylates NONO to terminate ATR-CHK1 signaling and that p97-ATX3 extracts RNF8 from chromatin to balance repair-pathway choice.

    Evidence In vitro ubiquitination, NONO lysine mutants, CHK1 timecourse, chromatin fractionation, survival assays

    PMID:30445466 PMID:31613024

    Open questions at the time
    • Trigger that switches RNF8 from signaling to self-limiting mode not defined
    • Selectivity of p97-ATX3 for chromatin RNF8 versus soluble pool unresolved
  23. 2023 High

    Linked RNF8 to transcription-replication conflict resolution and synthetic lethality, showing it ubiquitylates XRN2 to recruit it to R-loop-prone loci, with RNF8 loss causing R-loop accumulation in BRCA1-mutant cells.

    Evidence Co-IP, in vitro ubiquitination, ChIP-seq, R-loop immunofluorescence, synthetic lethality assays

    PMID:37697435

    Open questions at the time
    • Linkage type of XRN2 ubiquitination not specified
    • Therapeutic window of the synthetic lethality not tested
  24. 2017 Medium

    Defined cytoplasmic and signaling functions outside DNA repair, including PKM2-phospho-H3-directed H3 ubiquitination promoting glycolysis, neuronal cytoplasmic suppression of synapse differentiation, mitotic checkpoint scaffolding, and Twist-driven EMT.

    Evidence FHA mutants, ChIP, conditional neuronal knockouts, BioID proximity proteomics, and EMT/migration assays across separate studies

    PMID:27618486 PMID:28507061 PMID:29097665 PMID:37468549

    Open questions at the time
    • These context-specific functions rest largely on single-lab studies
    • How RNF8 partitions between nuclear and cytoplasmic roles not defined

Open questions

Synthesis pass · forward-looking unresolved questions
  • How RNF8 integrates its multiple E2 partners, chain types, and dozens of substrates into context-specific decisions — DNA repair pathway choice, telomere maintenance, meiotic chromatin remodeling, and cytoplasmic signaling — remains unresolved.
  • No unified model of E2/chain-type selection in different cellular contexts
  • Many proposed non-repair substrates (Slug, Akt, β-catenin, HDAC2) rest on low-confidence single-lab evidence
  • Quantitative dynamics of writer-eraser-extraction balance not established

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0016874 ligase activity 6 GO:0140096 catalytic activity, acting on a protein 6 GO:0140110 transcription regulator activity 2
Localization
GO:0000228 nuclear chromosome 3 GO:0005634 nucleus 3 GO:0005829 cytosol 3 GO:0005730 nucleolus 1 GO:0005815 microtubule organizing center 1
Pathway
R-HSA-73894 DNA Repair 6 R-HSA-4839726 Chromatin organization 5 R-HSA-1474165 Reproduction 3 R-HSA-1640170 Cell Cycle 3 R-HSA-392499 Metabolism of proteins 3 R-HSA-168256 Immune System 1
Partners
CHD4HERC2L3MBTL2MDC1RNF168UBC13UBCH8UBE2S
Complex memberships
CAMK2D-RNF8-MAD2 mitotic checkpoint complexRNF8-UBC13 ubiquitin ligase complex

Evidence

Reading pass · 50 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2007 RNF8 assembles at DNA double-strand breaks (DSBs) via interaction of its FHA domain with the phosphorylated adaptor protein MDC1, and its RING domain ubiquitin ligase activity ubiquitylates histones H2A and H2AX at DSB sites, promoting assembly of 53BP1 and BRCA1 repair proteins. Knockdown of RNF8 or disruption of its FHA or RING domains impaired DSB-associated ubiquitylation and inhibited retention of 53BP1 and BRCA1. RNF8 knockdown, FHA/RING domain mutants, immunofluorescence foci assays, ubiquitylation assays Cell High 18001824
2007 RNF8 FHA domain structure was solved by X-ray crystallography at 1.35 Å, establishing the structural basis for phospho-dependent binding of RNF8 to MDC1 and its role in ubiquitylating H2AX at damage sites. RNF8-depleted cells displayed a defective G2/M checkpoint and increased IR sensitivity. X-ray crystallography, RNF8 depletion, G2/M checkpoint assays, IR sensitivity Cell High 18001825
2007 RNF8 is recruited to DSBs through phospho-dependent interactions between its FHA domain and ATM-phosphorylated motifs in MDC1. RNF8, together with the E2 enzyme UBC13, promotes K63-linked ubiquitination, and depletion of UBC13 impairs 53BP1 recruitment, indicating RNF8 cooperates with UBC13 for DSB signaling. siRNA knockdown, co-immunoprecipitation, immunofluorescence, epistasis Science (New York, N.Y.) High 18006705
2007 RNF8, together with Ubc13, is required to generate K63-linked polyubiquitin chains that recruit the Brca1 A complex (Rap80/Abraxas/Brca1/Brcc36) to DNA damage sites. Rap80 UIM domains bind these K63-linked chains; Rap80 also contains an Abraxas-interacting region (AIR) required for assembly of the complex. siRNA knockdown, co-immunoprecipitation, domain mapping, ubiquitin-binding assays Proceedings of the National Academy of Sciences of the United States of America High 18077395
2006 RNF8 recruits UBC13 through its RING finger domain and can catalyze both K48- and K63-linked polyubiquitin chain formation in vitro, and co-localizes with UBC13 in the nucleus. Yeast two-hybrid, in vitro ubiquitination assays, nuclear co-localization by fluorescence Journal of cellular biochemistry Medium 16215985
2001 RNF8 interacts with class III E2 ubiquitin-conjugating enzymes (UBE2E2, UbcH6, UBE2E3) via its RING domain, catalyzes E2-dependent autoubiquitination in vitro, and localizes to the nucleus. A RING point mutant (C403S) shows markedly reduced ubiquitination activity. Yeast two-hybrid, in vitro ubiquitination assay, RING mutant analysis, GFP-fusion localization European journal of biochemistry Medium 11322894
2009 The Rap80-BRCC36 deubiquitinating enzyme complex antagonizes RNF8-Ubc13-dependent ubiquitination on chromatin at DSBs. Inhibition of BRCC36 partially restored DSB-associated ubiquitin levels following RNF8 knockdown and rescued 53BP1 recruitment, indicating that RNF8-Ubc13 ligase and BRCC36 hydrolase activities act in opposition to set steady-state ubiquitin levels at DSBs. RNF8 knockdown, BRCC36 knockdown, DUB-inactive mutant expression, immunofluorescence Proceedings of the National Academy of Sciences of the United States of America High 19202061
2009 RNF8 is recruited to NER-generated single-stranded UV-damage intermediates through interaction with MDC1 in an ATR-dependent, cell-cycle-independent manner, and RNF8 together with Ubc13 mediates sustained H2A ubiquitination at UV-damage sites, promoting 53BP1 and BRCA1 recruitment. Depletion causes UV hypersensitivity without affecting NER. siRNA knockdown, immunofluorescence, UV survival assays, cell cycle analysis The Journal of cell biology High 19797077
2010 RNF8-deficient mice are proficient in meiotic sex chromosome inactivation (MSCI) but deficient in global nucleosome removal during spermatogenesis. RNF8-dependent histone ubiquitination induces H4K16 acetylation, establishing a trans-histone modification cascade as an initial step in nucleosome removal. RNF8 knockout mouse model, immunofluorescence, histone modification analysis Developmental cell High 20153262
2010 ICP0, the herpes simplex virus type-1 E3 ubiquitin ligase, targets RNF8 (and RNF168) for degradation, resulting in loss of ubiquitinated H2A, mobilization of DNA repair proteins from damage sites, and enhanced viral fitness. ICP0 expression, immunoblot, immunofluorescence, viral fitness assays The EMBO journal High 20075863
2012 ICP0 mimics a cellular phosphosite by having CK1-phosphorylated T67, allowing it to bind the RNF8 FHA domain and recruit RNF8 for degradation, thereby promoting viral transcription and replication. This reveals a phosphorylation-mimicry mechanism by which a viral E3 hijacks RNF8. Phospho-mimicry mutant analysis, CK1 kinase assay, co-immunoprecipitation, viral replication assay Molecular cell High 22405594
2012 RNF168 acts with UBC13 to synthesize K63-linked ubiquitin chains at DSBs, whereas RNF8 primarily forms K48-linked chains on chromatin that promote substrate degradation. RNF8 regulates the abundance of the NHEJ factor KU80 at DSB sites via K48-linked ubiquitination, and RNF8 depletion results in prolonged KU80 retention and impaired NHEJ. Ubiquitin linkage-specific antibodies, K48/K63 ubiquitin mutants, RNF8/RNF168 knockdown, NHEJ assays, immunofluorescence Nature structural & molecular biology High 22266820
2012 RNF8 and RNF168 ubiquitinate KDM4A/JMJD2A, targeting it for proteasomal degradation after DNA damage. Loss of KDM4A permits 53BP1 access to dimethylated H4K20 at DSBs. Ectopic KDM4A expression abrogates 53BP1 foci, and combined KDM4A/KDM4B knockdown rescues 53BP1 foci in RNF8/RNF168-deficient cells. In vitro ubiquitination, proteasome inhibitor experiments, epistasis knockdown, immunofluorescence The EMBO journal High 22373579
2012 RNF8 exhibits a non-catalytic chromatin decondensation function via its FHA domain: RNF8 recruits CHD4 (catalytic subunit of NuRD complex) through a non-canonical FHA interaction, and CHD4 chromatin remodeling activity promotes efficient ubiquitin conjugation and assembly of RNF168 and BRCA1 at DSBs. This chromatin unfolding is independent of RNF8 ubiquitin ligase activity. RNF8 RING mutant, FHA domain interaction, CHD4 depletion, chromatin decondensation assay, immunofluorescence The EMBO journal High 22531782
2012 HERC2 is SUMOylated by PIAS4 at DSBs, and HERC2 SUMOylation is required for its DSB-induced association with RNF8, stabilizing the RNF8-Ubc13 complex. The ZZ zinc finger in HERC2 defines a novel SUMO-specific binding module; together with T4827 phosphorylation, it promotes HERC2 binding to RNF8. SUMO co-immunoprecipitation, PIAS4 knockdown, ZZ zinc finger mutants, immunofluorescence The Journal of cell biology High 22508508
2012 RNF8 ubiquitinates Nbs1 before and after DNA damage. RNF8 ubiquitination activity promotes optimal binding of Nbs1 to DSB-containing chromatin, and RNF8-mediated Nbs1 ubiquitination contributes to efficient and stable Nbs1 binding at DSBs and HR-mediated DSB repair. Co-immunoprecipitation, in vitro ubiquitination, laser microirradiation live-cell imaging, HR reporter assay The Journal of biological chemistry Medium 23115235
2012 RNF8 is required to recruit FAAP20, a Fanconi anemia core complex component with ubiquitin-binding activity, to interstrand crosslinks (ICLs). RNF8-UBC13-generated ubiquitin product is preferentially bound by FAAP20, and both RNF8 and FAAP20 are required for recruitment of FA core complex and FANCD2 to ICLs and for efficient FANCD2 monoubiquitination. Ubiquitin-binding assays, RNF8/FAAP20 depletion, immunofluorescence, FANCD2 monoubiquitination assay Molecular cell High 22705371
2011 RNF8 and Chfr synergistically regulate histone ubiquitination to control H4K16 acetylation via MRG15-dependent acetyltransferase complexes, thereby affecting chromatin relaxation and ATM activation in response to DNA damage. Double-knockout cells (RNF8/Chfr) show suppressed ATM activation, and DKO mice develop thymic lymphomas with chromosomal translocations. Double-knockout mouse model, ATM kinase assay, histone modification analysis, acetyltransferase complex co-immunoprecipitation Nature structural & molecular biology High 21706008
2011 RNF8 localizes to uncapped telomeres and promotes H2A ubiquitylation on telomeric chromatin, facilitating 53BP1 and phospho-ATM accumulation at uncapped telomeres and promoting NHEJ-mediated telomere fusions. Depletion of RNF8 reduces telomere-induced genome instability. RNF8 knockdown, immunofluorescence, telomere fusion assay, metaphase spreads Nature cell biology High 21857671
2011 Rnf8 E3 ubiquitin ligase physically interacts with Tpp1 (a shelterin component) and generates Ubc13-dependent K63 polyubiquitin chains on Tpp1 at lysine K233, stabilizing Tpp1 at telomeres. In Rnf8-deficient mice, Tpp1 is unstable, leading to telomere shortening and chromosome fusions via alternative NHEJ. Co-immunoprecipitation, in vitro ubiquitination, Rnf8 knockout mice, telomere length and fusion analysis Nature structural & molecular biology High 22101936
2008 RNF8 mono-ubiquitinates PCNA in the presence of UbcH5c and poly-ubiquitinates PCNA in the presence of Ubc13/Uev1a in vitro. RNF8 depletion suppressed both UV- and MNNG-stimulated mono-ubiquitination of PCNA in vivo. In vitro ubiquitination assay, RNF8 depletion by shRNA, PCNA ubiquitination immunoblot Cell cycle (Georgetown, Tex.) Medium 18948756
2012 RNF8 ubiquitinates p12 (the fourth subunit of DNA polymerase δ) using UbcH5c as the E2 enzyme, and DNA damage-induced p12 degradation is significantly reduced by shRNA knockdown of RNF8 in human cells and in RNF8-null mouse cells. RNF8 biochemical purification from HeLa cells, proteomics, in vitro ubiquitination, shRNA knockdown, p12 degradation immunoblot The Journal of biological chemistry Medium 23233665
2007 RNF8 protein levels peak in mitosis and decline in late mitotic stages. Overexpression of RNF8 causes a delay in cytokinesis and aberrant mitotic figures in a RING-domain-dependent (ubiquitin ligase activity-dependent) manner. RNF8 depletion delays exit from nocodazole-induced mitotic arrest and reduces cyclin B1 turnover. Cell-cycle synchronization, RNF8 overexpression and RING mutant expression, time-lapse imaging, cyclin B1 immunoblot Oncogene Medium 17724460
2010 RNF8 deficiency impairs immunoglobulin heavy chain class switch recombination (CSR) in a gene dose-dependent manner. H2AX and RNF8 function epistatically in CSR, and RNF8-deficient males are sterile due to defective ubiquitylation of XY chromatin. Partial 53BP1 recruitment at DSBs in activated Rnf8-null B cells reveals RNF8-independent mechanisms exist. RNF8 knockout mouse model, CSR assay, 53BP1 foci analysis, chromosome analysis The Journal of experimental medicine High 20385750
2012 RNF8-dependent ubiquitination of histone H2A during meiosis establishes active epigenetic modifications including H3K4 dimethylation on sex chromosomes, persisting through meiotic division. Subsequently, in post-meiotic spermatids, RNF8-dependent modifications include H3K4 trimethylation, histone lysine crotonylation, and H2AFZ incorporation, which are required for escape gene activation from the otherwise silent sex chromosomes. RNF8 knockout mice, ChIP-seq, RNA-seq, immunofluorescence Genes & development High 23249736
2013 JMJD1C demethylase is stabilized by interaction with RNF8, is recruited to DSBs, and demethylates MDC1 at Lys45, thereby promoting MDC1-RNF8 interaction, RNF8-dependent MDC1 ubiquitylation, and recruitment of RAP80-BRCA1 (but not 53BP1) to DSBs. Co-immunoprecipitation, JMJD1C depletion, methyl-lysine mass spectrometry, immunofluorescence Nature structural & molecular biology High 24240613
2011 RNF8 mediates K48-linked poly-ubiquitylation via interaction with UBCH8, while it mediates K63-linked poly-ubiquitylation via interaction with UBC13. A single point mutation (I405A) in the RNF8 RING domain selectively disrupts its interaction with UBCH8 and K48-based ubiquitylation while preserving UBC13 binding and K63-chain formation and downstream BRCA1/53BP1 assembly. RNF8 I405A RING mutant, in vitro ubiquitination assays, co-immunoprecipitation, immunofluorescence Nucleic acids research High 21911360
2018 L3MBTL2 is recruited to DSBs by MDC1 and is ubiquitylated by RNF8. Ubiquitylated L3MBTL2 in turn facilitates recruitment of RNF168 to the DNA lesion, identifying L3MBTL2 as the key link between RNF8 and RNF168 in the sequential ubiquitin signaling cascade. siRNA knockdown, co-immunoprecipitation, ubiquitylation assay, immunofluorescence, epistasis Nature cell biology High 29581593
2016 RNF8 crystal structure of its activated complex with Ubc13~ubiquitin was determined by X-ray crystallography and solution conformation by SAXS. RNF8 modulates conformations of ubiquitin linked to Ubc13 active site to stimulate K63-linked polyubiquitination. Structure-guided separation-of-function mutations show this E2-stimulating activity is essential for DSB signaling, 53BP1 recruitment, and BRCA1 recruitment. X-ray crystallography, SAXS, separation-of-function mutations, immunofluorescence in mammalian cells The Journal of biological chemistry High 26903517
2019 The p97/VCP unfoldase/segregase and the Ataxin 3 (ATX3) deubiquitinase form a physical and functional complex with RNF8 to regulate its proteasome-dependent homeostasis. Under genotoxic stress, the p97-ATX3 machinery stimulates extraction of RNF8 from chromatin to balance DNA repair pathway choice and promote cell survival. Co-immunoprecipitation, p97/ATX3 knockdown, RNF8 chromatin fractionation, IR survival assay, NHEJ assay The EMBO journal High 31613024
2017 RNF8 functions as a direct E3 ubiquitin ligase for Twist transcription factor, catalyzing K63-linked ubiquitination of Twist. This ubiquitination is required for Twist nuclear localization and subsequent EMT and cancer stem cell functions, conferring chemoresistance. E3 ligase screen, co-immunoprecipitation, in vitro ubiquitination, Twist localization assays, EMT/migration assays Molecular cell Medium 27618486
2017 RNF8 mediates K48-linked polyubiquitylation of histone H3 at K4 after EGF receptor activation via binding of its FHA domain to PKM2-phosphorylated H3-T11. H3 polyubiquitylation promotes histone dissociation, nucleosome disassembly, and RNA polymerase II binding to MYC and CCND1 promoters, promoting glycolysis and tumor cell proliferation. In vitro ubiquitination, co-immunoprecipitation, chromatin fractionation, ChIP, RNF8 FHA mutant, tumor growth assays The Journal of experimental medicine Medium 28507061
2017 RNF8 and Ube2S E2-conjugating enzyme are responsible for assembly of K11-linked ubiquitin conjugates on damaged chromatin (including H2A/H2AX) in an ATM-dependent manner. K11-linked ubiquitination regulates DNA damage-induced transcriptional silencing, distinct from K63-linked ubiquitin's role in recruiting 53BP1 and BRCA1. K11-linkage-specific antibodies, Ube2S/RNF8 knockdown, transcriptional silencing assay, chromatin fractionation Molecular cell High 28525740
2017 In neurons, RNF8 operates in the cytoplasm (unlike its nuclear role in proliferating cells) together with UBC13 to suppress synapse differentiation. Neuronal RNF8 interacts with HERC2 and scaffold protein NEURL4; knockdown of HERC2 or NEURL4 phenocopies RNF8/UBC13 loss on synapse differentiation. Granule neuron-specific RNF8 or UBC13 knockout impairs cerebellar-dependent learning. In vivo knockdown, conditional knockout in neurons, proteomics, immunofluorescence localization, synapse counting, behavioral assays Nature communications High 29097665
2019 RNF8 ubiquitinates NONO in response to UV damage, targeting NONO for proteasomal degradation. This degradation terminates ATR-CHK1 checkpoint signaling by blocking NONO-dependent chromatin loading of TOPBP1 (an ATR activator). RNF8 recruitment to UV-damage sites is ATR-dependent, placing RNF8-mediated NONO degradation in a negative feedback loop. Co-immunoprecipitation, in vitro ubiquitination, NONO lysine mutants, RNF8 depletion, CHK1 phosphorylation timecourse, clonogenic survival Nucleic acids research High 30445466
2018 RNF8 acts as a negative regulator of Notch1 signaling by ubiquitylating the active NOTCH1 intracellular domain (N1ICD), leading to its proteasomal degradation, thereby controlling cell-fate determination of mammary luminal progenitors and suppressing mammary tumorigenesis. Co-immunoprecipitation, ubiquitylation assay, RNF8-deficient mouse mammary epithelial cells, Notch1 target gene expression, tumorigenesis assay The Journal of clinical investigation Medium 30222135
2013 RNF8 localizes to centrosomes and cell division sites and promotes ubiquitylation of the septin SEPT7. RNF8 is evolutionary conserved as a homolog of yeast Dma1/Dma2 proteins, which ubiquitylate septins. Septin depletion increases cell division anomalies, linking RNF8 ubiquitylation activity to cytoplasmic septin regulation at division sites. Immunofluorescence localization, in vitro ubiquitination of septins, siRNA knockdown, cell division phenotype analysis Cell cycle (Georgetown, Tex.) Medium 23442799
2016 RNF8 conjugates K63-linked ubiquitin chains to tankyrase 1 in late S/G2 phase in a cell cycle-regulated manner. This ubiquitination stabilizes tankyrase 1, promotes its association with telomeres, and drives resolution of sister telomere cohesion. In G1 phase, the ABRO1/BRCC36 deubiquitinase complex removes these chains. Ubiquitin linkage-specific pulldown, RNF8 knockdown, cell cycle synchronization, telomere cohesion assay, tankyrase 1 stability analysis The EMBO journal Medium 27993934
2012 RNF8 and BRCA1 associate with the nucleolus in undamaged cells through RNF8 FHA domain interaction with the ribosomal protein RPSA. Following γ-irradiation, RNF8 and BRCA1 exit from the nucleolus to damage foci. Knockdown of RPSA depletes nucleolar RNF8/BRCA1 and impairs bulk protein translation. Immunofluorescence, RPSA co-immunoprecipitation, FRET, RPSA knockdown, protein synthesis assay Experimental cell research Medium 22814251
2004 RNF8 interacts with retinoid X receptor alpha (RXRα) through N-terminal regions of both proteins and co-localizes with RXRα in the nucleus. RNF8 dose-dependently enhances RXRα-mediated transactivation; this activity requires both the RING domain and the N-terminal region of RNF8. Yeast two-hybrid, pull-down assay, FRET, reporter gene assay, overexpression of RING and N-terminal mutants The Journal of biological chemistry Medium 14981089
2023 RNF8 ubiquitylates XRN2 (a factor required for transcription termination and R-loop resolution), facilitating XRN2 recruitment to R-loop-prone genomic loci. RNF8 deficiency in BRCA1-mutant breast cancer cells decreases XRN2 occupancy at R-loop-prone sites, promoting R-loop accumulation, transcription-replication collisions, and synthetic lethality. Co-immunoprecipitation, in vitro ubiquitination, ChIP-seq at R-loop loci, RNF8 knockdown in BRCA1-mutant cells, R-loop immunofluorescence, synthetic lethality assay Nucleic acids research High 37697435
2021 RNF8 directly interacts with and ubiquitinates RecQL4 DNA helicase at lysines 876, 1048, and 1101, promoting RecQL4 dissociation from DSB sites. RecQL4 ubiquitination mutants show prolonged DSB retention, hindering recruitment of CtIP and Ku80. WRAP53β scaffolds the RecQL4-RNF8 interaction and is required for RNF8 recruitment to DSBs. Co-immunoprecipitation, in vitro ubiquitination, site-directed mutagenesis, laser microirradiation, live-cell imaging, HR repair assay Oncogenesis Medium 33674555
2021 RNF8 ubiquitinates KMT5A (a histone H4K20 monomethyltransferase), promoting KMT5A recruitment to damaged chromatin. RNF8-induced KMT5A ubiquitination enhances KMT5A binding to RNF168. KMT5A then drives local H4K20 monomethylation at DSBs and promotes RNF168 H2A ubiquitination via its H2A acidic patch-interacting residues R188/R189. In vitro ubiquitination, co-immunoprecipitation, site-directed mutagenesis, ChIP, immunofluorescence, KMT5A R188/R189 mutant FASEB journal Medium 33710666
2017 DNA damage-induced ubiquitylation of histone H1 by HUWE1 is required to prime H1 for K63-linked chain elongation by RNF8-Ubc13. HUWE1 depletion reduces RNF168 and 53BP1 recruitment at damage sites while leaving MDC1 recruitment intact, positioning HUWE1-mediated H1 ubiquitylation upstream of RNF8 in the H1 poly-ubiquitylation pathway. Di-Gly proteomics, HUWE1 knockdown, RNF8/Ubc13 knockdown, immunofluorescence, epistasis Scientific reports Medium 29127375
2023 RNF8 competes with p31comet for binding to the closed conformer of MAD2 via its RING domain, while CAMK2D acts as a molecular scaffold concentrating the RNF8-MAD2 complex through interaction between CAMK2D p-Thr287 and the RNF8 FHA domain. This complex is required for mitotic checkpoint signaling; RNF8 overexpression impairs glioma stem cell mitotic progression in an FHA- and RING-dependent manner. RNF8 proximity proteomics (BioID), co-immunoprecipitation, domain mutant analysis (FHA/RING), mitotic progression assays, cell proliferation assays Cell death and differentiation Medium 37468549
2020 RNF8 directly interacts with β-catenin and facilitates its nuclear translocation by conjugating K63-linked polyubiquitination on it, leading to increased c-Myc expression and colon cancer proliferation. Co-immunoprecipitation, ubiquitination assay, nuclear fractionation, RNF8 overexpression and knockdown International journal of biological sciences Low 32549753
2022 RNF8 ubiquitinates HDAC2, promoting its degradation. Loss of HDAC2 de-represses Reelin expression (through altered H3K27me3 deacetylation at the Reelin promoter), leading to increased GSK3β-Ser9 phosphorylation and reduced GSK3β activity, protecting against ischemic neuronal damage. OGD/R neuronal model, MCAO mouse model, RNF8 knockdown, HDAC2 ubiquitination assay, Reelin promoter ChIP Molecular neurobiology Low 35622272
2021 RNF8 is the E3 ligase responsible for K63-linked ubiquitination of Akt, which activates Akt under physiological and genotoxic conditions, promoting lung cancer cell proliferation and resistance to chemotherapy. Co-immunoprecipitation, ubiquitination assay, RNF8 knockdown, Akt activity assay, clonogenic survival Cell reports Low 34686341
2020 RNF8 promotes K63-linked ubiquitination of Slug transcription factor, stabilizing Slug and activating EMT in lung cancer cells. Knockdown of Slug disrupts RNF8-dependent EMT, and RNF8 depletion inhibits metastasis in vivo. Co-immunoprecipitation, ubiquitination assay, Slug knockdown/overexpression rescue, EMT markers, xenograft model Molecular cancer research : MCR Low 32753472
2018 RNF8 and SCML2 cooperate in meiotic ubiquitination: RNF8 monoubiquitinates H2AK119, which is then deubiquitinated by SCML2 during meiosis. RNF8-dependent polyubiquitination (but not monoubiquitination) is required for H3K27 acetylation at active enhancers on sex chromosomes, linking RNF8 activity to sex chromosome epigenetic programming. RNF8/SCML2 double mutant mice, histone ChIP-seq, immunofluorescence, ubiquitination analysis PLoS genetics High 29462142

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2007 RNF8 ubiquitylates histones at DNA double-strand breaks and promotes assembly of repair proteins. Cell 939 18001824
2007 RNF8 transduces the DNA-damage signal via histone ubiquitylation and checkpoint protein assembly. Cell 839 18001825
2007 Orchestration of the DNA-damage response by the RNF8 ubiquitin ligase. Science (New York, N.Y.) 740 18006705
2007 Ubc13/Rnf8 ubiquitin ligases control foci formation of the Rap80/Abraxas/Brca1/Brcc36 complex in response to DNA damage. Proceedings of the National Academy of Sciences of the United States of America 357 18077395
2012 RNF8- and RNF168-dependent degradation of KDM4A/JMJD2A triggers 53BP1 recruitment to DNA damage sites. The EMBO journal 296 22373579
2010 RNF8-dependent histone modifications regulate nucleosome removal during spermatogenesis. Developmental cell 186 20153262
2009 The Rap80-BRCC36 de-ubiquitinating enzyme complex antagonizes RNF8-Ubc13-dependent ubiquitination events at DNA double strand breaks. Proceedings of the National Academy of Sciences of the United States of America 184 19202061
2012 The E3 ligase RNF8 regulates KU80 removal and NHEJ repair. Nature structural & molecular biology 172 22266820
2009 Nucleotide excision repair-induced H2A ubiquitination is dependent on MDC1 and RNF8 and reveals a universal DNA damage response. The Journal of cell biology 156 19797077
2010 A viral E3 ligase targets RNF8 and RNF168 to control histone ubiquitination and DNA damage responses. The EMBO journal 151 20075863
2013 The deubiquitylating enzyme USP44 counteracts the DNA double-strand break response mediated by the RNF8 and RNF168 ubiquitin ligases. The Journal of biological chemistry 117 23615962
2012 DNA damage-inducible SUMOylation of HERC2 promotes RNF8 binding via a novel SUMO-binding Zinc finger. The Journal of cell biology 113 22508508
2010 Rnf8 deficiency impairs class switch recombination, spermatogenesis, and genomic integrity and predisposes for cancer. The Journal of experimental medicine 101 20385750
2012 BAL1 and its partner E3 ligase, BBAP, link Poly(ADP-ribose) activation, ubiquitylation, and double-strand DNA repair independent of ATM, MDC1, and RNF8. Molecular and cellular biology 99 23230272
2012 RNF8 regulates active epigenetic modifications and escape gene activation from inactive sex chromosomes in post-meiotic spermatids. Genes & development 95 23249736
2012 A new non-catalytic role for ubiquitin ligase RNF8 in unfolding higher-order chromatin structure. The EMBO journal 93 22531782
2010 Recruitment of phosphorylated NPM1 to sites of DNA damage through RNF8-dependent ubiquitin conjugates. Cancer research 91 20713529
2016 The DNA Damage Transducer RNF8 Facilitates Cancer Chemoresistance and Progression through Twist Activation. Molecular cell 90 27618486
2018 L3MBTL2 orchestrates ubiquitin signalling by dictating the sequential recruitment of RNF8 and RNF168 after DNA damage. Nature cell biology 89 29581593
2011 Chfr and RNF8 synergistically regulate ATM activation. Nature structural & molecular biology 87 21706008
2006 The RING finger protein RNF8 recruits UBC13 for lysine 63-based self polyubiquitylation. Journal of cellular biochemistry 87 16215985
2013 JMJD1C demethylates MDC1 to regulate the RNF8 and BRCA1-mediated chromatin response to DNA breaks. Nature structural & molecular biology 86 24240613
2001 N-Terminally extended human ubiquitin-conjugating enzymes (E2s) mediate the ubiquitination of RING-finger proteins, ARA54 and RNF8. European journal of biochemistry 85 11322894
2010 Class switching and meiotic defects in mice lacking the E3 ubiquitin ligase RNF8. The Journal of experimental medicine 81 20385748
2008 PCNA is ubiquitinated by RNF8. Cell cycle (Georgetown, Tex.) 73 18948756
2009 Accumulation of Pax2 transactivation domain interaction protein (PTIP) at sites of DNA breaks via RNF8-dependent pathway is required for cell survival after DNA damage. The Journal of biological chemistry 68 19124460
2017 DNA damage-induced histone H1 ubiquitylation is mediated by HUWE1 and stimulates the RNF8-RNF168 pathway. Scientific reports 67 29127375
2008 RAP80 and RNF8, key players in the recruitment of repair proteins to DNA damage sites. Cancer letters 66 18550271
2011 DNA-damage response and repair activities at uncapped telomeres depend on RNF8. Nature cell biology 65 21857671
2012 Viral E3 ubiquitin ligase-mediated degradation of a cellular E3: viral mimicry of a cellular phosphorylation mark targets the RNF8 FHA domain. Molecular cell 63 22405594
2009 The RNF8/RNF168 ubiquitin ligase cascade facilitates class switch recombination. Proceedings of the National Academy of Sciences of the United States of America 62 20080757
2011 The E3 ubiquitin ligase Rnf8 stabilizes Tpp1 to promote telomere end protection. Nature structural & molecular biology 61 22101936
2012 A ubiquitin-binding protein, FAAP20, links RNF8-mediated ubiquitination to the Fanconi anemia DNA repair network. Molecular cell 59 22705371
2015 USP11 Is a Negative Regulator to γH2AX Ubiquitylation by RNF8/RNF168. The Journal of biological chemistry 57 26507658
2017 RNF8- and Ube2S-Dependent Ubiquitin Lysine 11-Linkage Modification in Response to DNA Damage. Molecular cell 55 28525740
2012 RNF8 regulates assembly of RAD51 at DNA double-strand breaks in the absence of BRCA1 and 53BP1. Cancer research 53 22865450
2019 The p97-Ataxin 3 complex regulates homeostasis of the DNA damage response E3 ubiquitin ligase RNF8. The EMBO journal 51 31613024
2011 Differential regulation of RNF8-mediated Lys48- and Lys63-based poly-ubiquitylation. Nucleic acids research 49 21911360
2018 RNF8 and SCML2 cooperate to regulate ubiquitination and H3K27 acetylation for escape gene activation on the sex chromosomes. PLoS genetics 48 29462142
2016 RNF8 promotes epithelial-mesenchymal transition of breast cancer cells. Journal of experimental & clinical cancer research : CR 48 27259701
2012 The RING finger protein RNF8 ubiquitinates Nbs1 to promote DNA double-strand break repair by homologous recombination. The Journal of biological chemistry 46 23115235
2011 RNF8-dependent histone ubiquitination during DNA damage response and spermatogenesis. Acta biochimica et biophysica Sinica 45 21444325
2018 Trabid inhibits hepatocellular carcinoma growth and metastasis by cleaving RNF8-induced K63 ubiquitination of Twist1. Cell death and differentiation 43 29748601
2008 RNF8-dependent and RNF8-independent regulation of 53BP1 in response to DNA damage. The Journal of biological chemistry 39 18337245
2013 Put a RING on it: regulation and inhibition of RNF8 and RNF168 RING finger E3 ligases at DNA damage sites. Frontiers in genetics 38 23847653
2007 Regulation of mitotic exit by the RNF8 ubiquitin ligase. Oncogene 38 17724460
2021 RNF8-mediated regulation of Akt promotes lung cancer cell survival and resistance to DNA damage. Cell reports 37 34686341
2014 Rad18 and Rnf8 facilitate homologous recombination by two distinct mechanisms, promoting Rad51 focus formation and suppressing the toxic effect of nonhomologous end joining. Oncogene 36 25417706
2004 The RING finger protein, RNF8, interacts with retinoid X receptor alpha and enhances its transcription-stimulating activity. The Journal of biological chemistry 36 14981089
2017 RNF8 mediates histone H3 ubiquitylation and promotes glycolysis and tumorigenesis. The Journal of experimental medicine 35 28507061
2017 RNF8/UBC13 ubiquitin signaling suppresses synapse formation in the mammalian brain. Nature communications 35 29097665
2016 RNF8 E3 Ubiquitin Ligase Stimulates Ubc13 E2 Conjugating Activity That Is Essential for DNA Double Strand Break Signaling and BRCA1 Tumor Suppressor Recruitment. The Journal of biological chemistry 34 26903517
2012 Identification of RNF8 as a ubiquitin ligase involved in targeting the p12 subunit of DNA polymerase δ for degradation in response to DNA damage. The Journal of biological chemistry 34 23233665
2016 Cell cycle-regulated ubiquitination of tankyrase 1 by RNF8 and ABRO1/BRCC36 controls the timing of sister telomere resolution. The EMBO journal 33 27993934
2019 RNF8 mediates NONO degradation following UV-induced DNA damage to properly terminate ATR-CHK1 checkpoint signaling. Nucleic acids research 32 30445466
2017 RNF8 identified as a co-activator of estrogen receptor α promotes cell growth in breast cancer. Biochimica et biophysica acta. Molecular basis of disease 32 28216286
2016 RNF168 cooperates with RNF8 to mediate FOXM1 ubiquitination and degradation in breast cancer epirubicin treatment. Oncogenesis 32 27526106
2012 MDC1 and RNF8 function in a pathway that directs BRCA1-dependent localization of PALB2 required for homologous recombination. Journal of cell science 32 23038782
2018 Ubiquitin ligase RNF8 suppresses Notch signaling to regulate mammary development and tumorigenesis. The Journal of clinical investigation 31 30222135
2016 Opposing roles of RNF8/RNF168 and deubiquitinating enzymes in ubiquitination-dependent DNA double-strand break response signaling and DNA-repair pathway choice. Journal of radiation research 30 26983989
2011 Critical roles of ring finger protein RNF8 in replication stress responses. The Journal of biological chemistry 30 21558560
2020 RNF8 induces β-catenin-mediated c-Myc expression and promotes colon cancer proliferation. International journal of biological sciences 29 32549753
2020 Silica nanoparticles induce spermatogenesis disorders via L3MBTL2-DNA damage-p53 apoptosis and RNF8-ubH2A/ubH2B pathway in mice. Environmental pollution (Barking, Essex : 1987) 29 32554096
2019 The Functions of DNA Damage Factor RNF8 in the Pathogenesis and Progression of Cancer. International journal of biological sciences 28 31182912
2014 Regulation of 53BP1 protein stability by RNF8 and RNF168 is important for efficient DNA double-strand break repair. PloS one 28 25337968
2014 miR-214-mediated downregulation of RNF8 induces chromosomal instability in ovarian cancer cells. Cell cycle (Georgetown, Tex.) 28 25483088
2012 Nucleolar exit of RNF8 and BRCA1 in response to DNA damage. Experimental cell research 26 22814251
2018 Function of RAD6B and RNF8 in spermatogenesis. Cell cycle (Georgetown, Tex.) 24 28825854
2013 Dma/RNF8 proteins are evolutionarily conserved E3 ubiquitin ligases that target septins. Cell cycle (Georgetown, Tex.) 23 23442799
2012 RNF8 and RNF168 but not HERC2 are required for DNA damage-induced ubiquitylation in chicken DT40 cells. DNA repair 22 23010445
2023 RNF8 ubiquitylation of XRN2 facilitates R-loop resolution and restrains genomic instability in BRCA1 mutant cells. Nucleic acids research 21 37697435
2020 RNF8 Promotes Epithelial-Mesenchymal Transition in Lung Cancer Cells via Stabilization of Slug. Molecular cancer research : MCR 21 32753472
2019 Bioinformatic Identification of miR-622 Key Target Genes and Experimental Validation of the miR-622-RNF8 Axis in Breast Cancer. Frontiers in oncology 21 31709182
2016 The role of HERC2 and RNF8 ubiquitin E3 ligases in the promotion of translesion DNA synthesis in the chicken DT40 cell line. DNA repair 20 26994443
2016 NRAGE is involved in homologous recombination repair to resist the DNA-damaging chemotherapy and composes a ternary complex with RNF8-BARD1 to promote cell survival in squamous esophageal tumorigenesis. Cell death and differentiation 20 27035619
2015 ATDC (Ataxia Telangiectasia Group D Complementing) Promotes Radioresistance through an Interaction with the RNF8 Ubiquitin Ligase. The Journal of biological chemistry 19 26381412
2020 RNF8 has both KU-dependent and independent roles in chromosomal break repair. Nucleic acids research 18 32427332
2015 RNF8 deficiency results in neurodegeneration in mice. Neurobiology of aging 18 26256786
2017 Interaction between RNF8 and DYRK2 is required for the recruitment of DNA repair molecules to DNA double-strand breaks. FEBS letters 17 28194753
2013 Synergistic interaction of Rnf8 and p53 in the protection against genomic instability and tumorigenesis. PLoS genetics 17 23382699
2020 RNF8 induces autophagy and reduces inflammation by promoting AKT degradation via ubiquitination in ulcerative colitis mice. Journal of biochemistry 16 32597970
2021 RNF8 ubiquitinates RecQL4 and promotes its dissociation from DNA double strand breaks. Oncogenesis 15 33674555
2019 Corilagin Inhibits Esophageal Squamous Cell Carcinoma by Inducing DNA Damage and Down-Regulation of RNF8. Anti-cancer agents in medicinal chemistry 15 30848215
2016 Adenovirus-mediated downregulation of the ubiquitin ligase RNF8 sensitizes bladder cancer to radiotherapy. Oncotarget 15 26788910
2015 Ubiquitin-H2AX fusions render 53BP1 recruitment to DNA damage sites independent of RNF8 or RNF168. Cell cycle (Georgetown, Tex.) 15 25695757
2013 RNAi silencing targeting RNF8 enhances radiosensitivity of a non-small cell lung cancer cell line A549. International journal of radiation biology 14 23578064
2022 RNF8 up-regulates AR/ARV7 action to contribute to advanced prostate cancer progression. Cell death & disease 13 35428760
2019 miR-214 inhibits epithelial-mesenchymal transition of breast cancer cells via downregulation of RNF8. Acta biochimica et biophysica Sinica 13 31294443
2015 The proximity ligation assay reveals that at DNA double-strand breaks WRAP53β associates with γH2AX and controls interactions between RNF8 and MDC1. Nucleus (Austin, Tex.) 13 26734725
2022 Neuroprotective Effect of E3 Ubiquitin Ligase RNF8 Against Ischemic Stroke via HDAC2 Stability Reduction and Reelin-Dependent GSK3β Inhibition. Molecular neurobiology 12 35622272
2014 BCL10 regulates RNF8/RNF168-mediated ubiquitination in the DNA damage response. Cell cycle (Georgetown, Tex.) 12 24732096
2012 Three-dimensional imaging reveals the spatial separation of γH2AX-MDC1-53BP1 and RNF8-RNF168-BRCA1-A complexes at ionizing radiation-induced foci. Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology 12 22633816
2025 ZNF451 collaborates with RNF8 to regulate RNF168 localization and amplify ubiquitination signaling to promote DNA damage repair and regulate radiosensitivity. Cell death and differentiation 11 40055579
2021 RNF8-ubiquitinated KMT5A is required for RNF168-induced H2A ubiquitination in response to DNA damage. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 11 33710666
2021 The RNF8 and RNF168 Ubiquitin Ligases Regulate Pro- and Anti-Resection Activities at Broken DNA Ends During Non-Homologous End Joining. DNA repair 11 34481157
2020 RNF8 Dysregulation and Down-regulation During HTLV-1 Infection Promote Genomic Instability in Adult T-Cell Leukemia. PLoS pathogens 11 32453758
2023 CAMK2D serves as a molecular scaffold for RNF8-MAD2 complex to induce mitotic checkpoint in glioma. Cell death and differentiation 10 37468549
2012 Fusing telomeres with RNF8. Nucleus (Austin, Tex.) 10 22555600
2023 miR-146a-5p regulates autophagy and NLRP3 inflammasome activation in epithelial barrier damage in the in vitro cell model of ulcerative colitis through the RNF8/Notch1/mTORC1 pathway. Immunobiology 9 37329823
2021 Targeting RNF8 effectively reverses cisplatin and doxorubicin resistance in endometrial cancer. Biochemical and biophysical research communications 9 33548629

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