Affinage

RNF8

E3 ubiquitin-protein ligase RNF8 · UniProt O76064

Length
485 aa
Mass
55.5 kDa
Annotated
2026-04-28
100 papers in source corpus 48 papers cited in narrative 47 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

RNF8 is a RING-finger E3 ubiquitin ligase that serves as a master coordinator of the DNA damage response ubiquitin signaling cascade, with additional roles in spermatogenesis, telomere maintenance, mitotic regulation, and transcriptional control. At DNA double-strand breaks, its FHA domain binds ATM-phosphorylated MDC1, and its RING domain engages multiple E2 conjugating enzymes—UBC13 for K63-linked chains, UBCH8 for K48-linked chains, and Ube2S for K11-linked chains—to ubiquitinate histones H2A/H2AX, L3MBTL2, JMJD2A, KU80, and other substrates, thereby orchestrating chromatin remodeling via CHD4/NuRD, RNF168 recruitment, 53BP1 and BRCA1-A complex assembly, proteasomal substrate clearance, and damage-induced transcriptional silencing (PMID:18001824, PMID:22266820, PMID:28525740, PMID:29581593, PMID:22531782). Beyond DSB signaling, RNF8-dependent histone ubiquitination drives trans-histone crosstalk to H4K16 acetylation required for nucleosome removal during spermatogenesis, ubiquitinates TPP1 to stabilize the shelterin complex at telomeres, and ubiquitinates tankyrase 1 for cell-cycle-regulated sister telomere resolution (PMID:20153262, PMID:22101936, PMID:27993934). RNF8 also functions in growth factor signaling by recognizing PKM2-phosphorylated histone H3-T11 via its FHA domain to catalyze K48-linked H3 ubiquitination and nucleosome disassembly at oncogene promoters, and ubiquitinates Twist1 with K63-linked chains to promote EMT (PMID:28507061, PMID:27618486).

Mechanistic history

Synthesis pass · year-by-year structured walk · 15 steps
  1. 2001 Medium

    Establishing that RNF8 is a nuclear RING-type E3 ubiquitin ligase resolved its basic biochemical identity: the RING domain engages class III E2 enzymes and is required for autoubiquitination activity.

    Evidence Yeast two-hybrid, in vitro ubiquitylation, RING C403S mutant, GFP localization in COS-7 cells

    PMID:11322894

    Open questions at the time
    • Physiological substrates unknown
    • In vivo function not addressed
    • Single lab study
  2. 2004 Medium

    Before its DNA damage role was discovered, RNF8 was identified as a coactivator of RXRα-mediated transcription, establishing an early link between its RING-dependent ligase activity and nuclear receptor signaling.

    Evidence Yeast two-hybrid, FRET, reporter transactivation assays with RING point mutants

    PMID:14981089

    Open questions at the time
    • RXRα ubiquitination not directly demonstrated
    • Physiological relevance in vivo not tested
    • Single lab study
  3. 2006 Medium

    Demonstrating that RNF8 recruits UBC13 to generate K63-linked polyubiquitin chains (and other E2s for K48-linked chains) established its capacity for linkage-specific ubiquitin chain assembly, presaging its bifunctional role at DNA damage sites.

    Evidence Yeast two-hybrid, in vitro ubiquitylation with UBC13

    PMID:16215985

    Open questions at the time
    • Cellular substrates of K63 chains not identified
    • Single lab study
  4. 2007 High

    Three simultaneous studies revealed RNF8 as a central hub of the DSB ubiquitin signaling cascade: its FHA domain binds ATM-phosphorylated MDC1 to target it to breaks, and its RING/UBC13-dependent K63-linked ubiquitination of H2A/H2AX recruits 53BP1 and the BRCA1-A complex (via RAP80 UIMs), resolving how histone ubiquitination bridges damage detection to repair factor assembly.

    Evidence FHA/RING mutagenesis, RNF8 knockdown, co-IP, immunofluorescence foci, in vitro ubiquitylation, crystal structure of FHA domain at 1.35 Å

    PMID:18001824 PMID:18001825 PMID:18006705 PMID:18077395

    Open questions at the time
    • How RNF8 cooperates with RNF168 not yet defined
    • Identity of ubiquitinated histone residues at breaks not mapped
    • Contribution of non-K63 chain types at DSBs unknown
  5. 2007 Medium

    RNF8 overexpression delays cytokinesis and its depletion impairs mitotic exit with reduced cyclin B1 turnover, indicating a ligase-dependent mitotic function independent of its DNA damage role.

    Evidence Overexpression/RING mutant, RNF8 depletion, time-lapse microscopy, cyclin B1 degradation assay

    PMID:17724460

    Open questions at the time
    • Direct mitotic substrate not identified
    • Mechanism linking RNF8 to cyclin B1 turnover unclear
    • Single lab study
  6. 2009 High

    Two advances extended RNF8's reach: BRCC36 deubiquitinase was shown to oppose RNF8-UBC13 ubiquitination at DSBs (establishing dynamic ubiquitin homeostasis at damage sites), and RNF8 was recruited to UV-induced NER lesions via ATR/MDC1, generalizing its function beyond DSBs.

    Evidence BRCC36 catalytic mutant, knockdown epistasis, UV foci assays, cell cycle analysis

    PMID:19202061 PMID:19797077

    Open questions at the time
    • Whether RNF8 chain topology differs at NER vs DSB sites not resolved
    • How BRCC36 access is regulated at breaks unknown
  7. 2010 High

    Rnf8 knockout mice revealed that RNF8-dependent histone ubiquitination in spermatids triggers H4K16 acetylation required for global nucleosome removal during spermatogenesis, establishing a trans-histone crosstalk mechanism with essential developmental consequences.

    Evidence Rnf8 knockout mice, chromatin fractionation, histone modification western blot/IF

    PMID:20153262

    Open questions at the time
    • Identity of histone acetyltransferase bridging ubiquitin to H4K16ac not fully defined
    • Whether ubiquitin chain type matters for crosstalk not tested
  8. 2011 High

    A separation-of-function RING mutant (I405A) demonstrated that RNF8 uses distinct E2 interfaces for K48 (UBCH8) versus K63 (UBC13) chain assembly, and RNF8 was shown at uncapped telomeres where it ubiquitinates TPP1-K233 to stabilize shelterin and facilitate NHEJ of dysfunctional telomere ends.

    Evidence I405A separation-of-function mutant, linkage-specific in vitro assays, telomere dysfunction-induced foci, chromosome fusion analysis, TPP1-K233R mutant

    PMID:21857671 PMID:21911360 PMID:22101936

    Open questions at the time
    • Full set of K48-linked substrates at DSBs not catalogued
    • TPP1 ubiquitination role in normal (capped) telomere homeostasis not examined
  9. 2012 High

    A burst of substrate discovery resolved how RNF8 clears inhibitory proteins from damage sites and coordinates repair pathway choice: RNF8 K48-ubiquitinates KU80 and JMJD2A for proteasomal degradation (unmasking H4K20me2 for 53BP1), mediates chromatin decondensation through non-catalytic FHA-CHD4/NuRD interaction, ubiquitinates Nbs1 for HR, p12 for Pol δ remodeling, and FAAP20 for Fanconi anemia ICL repair; HERC2 SUMOylation stabilizes the RNF8-UBC13 complex; and RNF8 drives meiotic epigenetic memory on sex chromosomes.

    Evidence Linkage-specific antibodies, in vitro ubiquitylation, separation-of-function mutants, CHD4 depletion, KO mice with ChIP-seq, ICL repair assays

    PMID:22266820 PMID:22373579 PMID:22508508 PMID:22531782 PMID:22705371 PMID:23115235 PMID:23233665 PMID:23249736

    Open questions at the time
    • How RNF8 selects among competing substrates at a single DSB not understood
    • Relative contributions of K48 vs K63 chains to repair outcome not quantitated in vivo
    • Whether CHD4 interaction is regulated independently of FHA-phospho binding unclear
  10. 2016 High

    Crystal structure of the RNF8 RING–UBC13~ubiquitin complex revealed how RNF8 stimulates polyubiquitin chain elongation by repositioning the donor ubiquitin on UBC13, and RNF8 was found to ubiquitinate Twist1 with K63 chains to drive EMT/cancer stemness and tankyrase 1 for cell-cycle-regulated telomere cohesion resolution.

    Evidence X-ray crystallography, SAXS, separation-of-function mutagenesis, EMT functional readouts, cell cycle fractionation, telomere cohesion assays

    PMID:26903517 PMID:27618486 PMID:27993934

    Open questions at the time
    • Whether RNF8 stimulatory mechanism generalizes to other RING-E2 pairs not tested
    • Twist1 ubiquitination site not mapped
    • Upstream signals triggering RNF8-tankyrase interaction not defined
  11. 2017 High

    Three new dimensions of RNF8 function emerged: K11-linked chains (via Ube2S) on histones mediate transcriptional silencing at DSBs distinct from K63-chain signaling; FHA domain recognition of PKM2-phosphorylated H3-T11 directs K48-linked H3 ubiquitination for nucleosome disassembly at EGF-responsive gene promoters; and cytoplasmic RNF8 in neurons suppresses synapse differentiation via HERC2/NEURL4-scaffolded UBC13-dependent ubiquitination.

    Evidence K11 linkage-specific antibodies, transcription reporter, FHA-phosphopeptide binding, ChIP, conditional neuronal KO, electrophysiology, behavioral assays

    PMID:28507061 PMID:28525740 PMID:29097665

    Open questions at the time
    • K11-chain substrate identity at DSBs not defined beyond histones
    • Whether H3 ubiquitination by RNF8 at promoters is genome-wide or locus-specific not resolved
    • Neuronal RNF8 substrates not identified
  12. 2018 High

    L3MBTL2 was identified as the missing substrate linking RNF8 to RNF168 recruitment: RNF8 ubiquitinates L3MBTL2, whose ubiquitinated form recruits RNF168 to DSBs, resolving a long-standing gap in the sequential ubiquitin cascade. Separately, RNF8 K48-ubiquitinates NOTCH1 intracellular domain to negatively regulate Notch signaling in mammary progenitors.

    Evidence In vitro ubiquitylation, L3MBTL2 depletion, epistasis with RNF168, Rnf8 KO mammary gland, Notch reporter

    PMID:29581593 PMID:30222135

    Open questions at the time
    • L3MBTL2 ubiquitination sites not mapped
    • Whether L3MBTL2 is the sole bridge to RNF168 or acts in parallel with H1 ubiquitination not resolved
  13. 2019 High

    Post-translational regulation of RNF8 itself was clarified: p97/VCP-Ataxin3 controls RNF8 steady-state levels and extracts it from chromatin to balance repair; RNF8 ubiquitinates NONO to terminate ATR-CHK1 checkpoint signaling, establishing a negative feedback loop after UV damage.

    Evidence Co-IP, chromatin fractionation, proteasome inhibitor, NONO lysine mutants, CHK1 phosphorylation kinetics

    PMID:30445466 PMID:31613024

    Open questions at the time
    • How p97-ATX3 is recruited specifically to RNF8 not clear
    • NONO ubiquitination sites not fully mapped
  14. 2021 Medium

    RNF8's substrate repertoire expanded to RecQL4 (ubiquitination promotes its removal from DSBs to permit CtIP/Ku80 access) and KMT5A/PR-Set7 (ubiquitination drives local H4K20me1 that enhances RNF168-catalyzed H2A ubiquitination), further detailing how RNF8 coordinates sequential chromatin transactions at breaks.

    Evidence In vitro ubiquitylation, site-directed mutants, laser microirradiation, ChIP, H2A ubiquitination assay

    PMID:33674555 PMID:33710666

    Open questions at the time
    • RecQL4 and KMT5A studies are each from single labs
    • In vivo physiological importance of these modifications not tested in animal models
  15. 2023 High

    RNF8 was found to ubiquitinate XRN2 to promote its recruitment to R-loop-prone loci, with RNF8 loss in BRCA1-mutant cells causing R-loop accumulation and synthetic lethality; separately, RNF8 was linked to mitotic checkpoint regulation through RING-dependent interaction with closed-MAD2 scaffolded by phospho-CAMK2D.

    Evidence In vitro ubiquitylation, ChIP-seq, DRIP-seq, clonogenic survival; proximity proteomics, CAMK2D phospho-mutants, live-cell mitosis imaging

    PMID:37468549 PMID:37697435

    Open questions at the time
    • XRN2 ubiquitination sites not mapped
    • Therapeutic potential of RNF8 synthetic lethality with BRCA1 not tested in vivo
    • MAD2-RNF8 interaction lacks in vitro reconstitution of checkpoint function

Open questions

Synthesis pass · forward-looking unresolved questions
  • Major open questions include: how RNF8 selects among its many substrates at a single damage site, the relative in vivo contributions of K63/K48/K11 chain types to different repair outcomes, the structural basis of FHA-domain substrate selectivity beyond MDC1, and whether the neuronal and transcriptional functions of RNF8 are mechanistically linked to its chromatin-remodeling activities.
  • No integrated structural model of full-length RNF8 with substrates
  • Substrate prioritization mechanism at damage sites unknown
  • In vivo chain-type-specific requirements not genetically separated

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140096 catalytic activity, acting on a protein 19 GO:0016874 ligase activity 6 GO:0042393 histone binding 5
Localization
GO:0005634 nucleus 5 GO:0005694 chromosome 5 GO:0005730 nucleolus 1 GO:0005829 cytosol 1
Pathway
R-HSA-73894 DNA Repair 16 R-HSA-392499 Metabolism of proteins 7 R-HSA-4839726 Chromatin organization 5 R-HSA-162582 Signal Transduction 3 R-HSA-1640170 Cell Cycle 3 R-HSA-1474165 Reproduction 2 R-HSA-112316 Neuronal System 1
Complex memberships
HERC2-NEURL4-RNF8RNF8-UBC13

Evidence

Reading pass · 47 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2007 RNF8 assembles at DNA double-strand breaks (DSBs) via its FHA domain binding to phosphorylated MDC1, and its RING domain ubiquitin ligase activity ubiquitylates histone H2A and H2AX at DSB sites, promoting accumulation of 53BP1 and BRCA1 repair proteins. Disruption of either FHA or RING domain impairs DSB-associated ubiquitylation and repair factor retention. FHA/RING domain mutagenesis, RNF8 knockdown, co-immunoprecipitation, immunofluorescence foci assays, in vitro ubiquitylation Cell High 18001824 18001825 18006705
2007 Crystal structure of the RNF8 FHA domain resolved at 1.35 Å, establishing structural basis for phospho-dependent interaction with MDC1 which is phosphorylated by ATM kinase. X-ray crystallography Cell High 18001825
2007 RNF8 cooperates with the E2-conjugating enzyme UBC13 to generate K63-linked polyubiquitin chains at DSBs, which are recognized by the UIM domains of RAP80, recruiting the entire BRCA1-A complex (BRCA1/BARD1/Abraxas/RAP80/BRCC36) to damage sites. Co-immunoprecipitation, UBC13 depletion, immunofluorescence foci assays Science; PNAS High 18006705 18077395
2006 RNF8 recruits UBC13 through its RING domain to catalyze K63-linked polyubiquitin chains, and can also engage other E2s to catalyze K48-linked chains; RNF8 co-localizes with UBC13 in the nucleus. Yeast two-hybrid, in vitro ubiquitylation assay, co-localization by fluorescence microscopy Journal of cellular biochemistry Medium 16215985
2001 RNF8 interacts with class III E2 ubiquitin-conjugating enzymes (UBE2E2, UbcH6, UBE2E3) through its RING domain, and the RING domain is required for E2-dependent autoubiquitination activity in vitro. RNF8 localizes to the nucleus. Yeast two-hybrid, in vitro ubiquitylation assay, RING point mutant (C403S), GFP localization in COS-7 cells European journal of biochemistry Medium 11322894
2009 The BRCC36 deubiquitinase within the RAP80-BRCC36 complex opposes RNF8-Ubc13-dependent ubiquitination at DSBs, establishing that steady-state ubiquitin levels at DSBs are determined by opposing RNF8-Ubc13 ligase and BRCC36 hydrolase activities. RNF8 knockdown, BRCC36 knockdown, BRCC36 catalytic mutant expression, immunofluorescence, γH2AX ubiquitination assay PNAS High 19202061
2009 RNF8 is recruited to sites of UV-induced nucleotide excision repair lesions through interaction with MDC1, in an ATR-dependent and cell cycle-independent manner, where it promotes H2A ubiquitination via Ubc13. RNF8/Ubc13 depletion, UV damage foci assays, MDC1 co-immunoprecipitation, cell cycle analysis Journal of Cell Biology High 19797077
2010 RNF8-dependent histone ubiquitination in spermatids induces H4K16 acetylation (trans-histone cross-talk), which is required for global nucleosome removal during spermatogenesis. RNF8-deficient mice are proficient in MSCI but deficient in global nucleosome removal. RNF8 knockout mice, chromatin fractionation, histone modification analysis by western blot and immunofluorescence Developmental Cell High 20153262
2010 Herpes simplex virus ICP0, an E3 ubiquitin ligase, targets RNF8 (and RNF168) for proteasomal degradation, resulting in loss of H2A ubiquitination and mobilization of DNA repair proteins, thereby hijacking the cellular DSB response. Co-immunoprecipitation, western blot for protein degradation, immunofluorescence, viral fitness assays EMBO Journal High 20075863
2012 RNF8 primarily forms K48-linked ubiquitin chains on chromatin at DSBs (distinct from RNF168 which forms K63-linked chains via UBC13), promoting proteasomal degradation of substrates including KU80, thereby regulating KU80 removal and non-homologous end-joining. Ubiquitin linkage-specific antibodies, in vitro ubiquitylation, RNF8/RNF168 knockdown, live-cell imaging of KU80 at damage sites Nature Structural & Molecular Biology High 22266820
2012 RNF8 and RNF168 ubiquitinate JMJD2A/KDM4A, triggering its proteasomal degradation at DSB sites. JMJD2A normally competes with 53BP1 for binding to H4K20me2; its RNF8-dependent degradation unmasks H4K20me2 to allow 53BP1 recruitment. Ubiquitination assay, proteasome inhibitor treatment, JMJD2A overexpression rescue, combined JMJD2A/2B knockdown in RNF8/168-deficient cells EMBO Journal High 22373579
2012 RNF8 mediates chromatin decondensation at DSBs through a non-catalytic (ubiquitin ligase-independent) interaction via its FHA domain with CHD4, the catalytic subunit of the NuRD chromatin remodeling complex. CHD4-mediated chromatin remodeling promotes efficient RNF168 and BRCA1 assembly at DSBs. RING/FHA domain mutants, CHD4 depletion, chromatin decondensation assay, co-immunoprecipitation, immunofluorescence EMBO Journal High 22531782
2012 HERC2 undergoes DNA damage-induced SUMOylation by PIAS4; SUMOylated HERC2, together with phosphorylation at T4827, binds RNF8 via the HERC2 ZZ zinc finger (a novel SUMO-binding module), stabilizing the RNF8-Ubc13 complex at DSBs. Co-immunoprecipitation, SUMO site mapping, ZZ domain mutants, PIAS4 depletion, in vitro SUMO-binding assay Journal of Cell Biology High 22508508
2011 RNF8 and Chfr synergistically regulate histone ubiquitination to control H4K16 acetylation via MRG15-dependent acetyltransferase complexes, which in turn promotes chromatin relaxation and ATM kinase activation in response to DNA damage. DKO cells show suppressed ATM activation. Double-knockout mice, chromatin relaxation assay, acetylation western blot, MRG15 co-immunoprecipitation, ATM kinase assay Nature Structural & Molecular Biology High 21706008
2008 RNF8 ubiquitinates PCNA in vitro with UbcH5c (monoubiquitination) and with Ubc13/Uev1a (polyubiquitination), mirroring Rad18/Rad6 and Rad5/Ubc13 activities, and RNF8 depletion suppresses UV- and MNNG-stimulated PCNA mono-ubiquitination in vivo. In vitro ubiquitylation assay, RNF8 shRNA depletion, western blot for ubiquitinated PCNA Cell Cycle Medium 18948756
2011 Rnf8 localizes to uncapped telomeres and promotes accumulation of 53BP1 and phospho-ATM at deprotected telomeres via H2A ubiquitylation, facilitating non-homologous end-joining of dysfunctional telomere ends. RNF8 depletion, telomere dysfunction-induced foci (TIF) assay, chromosome fusions by metaphase analysis Nature Cell Biology High 21857671
2011 Rnf8 physically interacts with Tpp1 and generates Ubc13-dependent K63-linked polyubiquitin chains on Tpp1 at Lys233, stabilizing Tpp1 at telomeres. The RING domain of Rnf8 is essential for Tpp1 stability and telomere end protection. Co-immunoprecipitation, in vitro ubiquitylation, RING domain mutant, K233R Tpp1 mutant, telomere-FISH, chromosome end-to-end fusion analysis Nature Structural & Molecular Biology High 22101936
2012 RNF8 directly ubiquitinates Nbs1 both before and after DNA damage; RNF8 ubiquitination of Nbs1 promotes Nbs1's stable binding to DSB-containing chromatin and is required for efficient homologous recombination. Co-immunoprecipitation, in vitro ubiquitylation, laser microirradiation + live-cell imaging, HR repair assay Journal of Biological Chemistry Medium 23115235
2012 RNF8 ubiquitinates FAAP20; this ubiquitin signal is recognized by FAAP20's ubiquitin-binding domain to recruit the Fanconi anemia core complex and FANCD2 to interstrand crosslink sites, enabling FANCD2 monoubiquitination and ICL repair. Co-immunoprecipitation, in vitro ubiquitylation, FAAP20 UBD mutations, FANCD2 monoubiquitination assay, ICL sensitivity assays Molecular Cell High 22705371
2013 JMJD1C demethylates MDC1 at Lys45, promoting MDC1-RNF8 interaction and RNF8-dependent MDC1 ubiquitylation. JMJD1C is stabilized by its interaction with RNF8 and is required for RAP80-BRCA1 but not 53BP1 recruitment to DSBs. Co-immunoprecipitation, demethylation assay, JMJD1C depletion, immunofluorescence foci assays Nature Structural & Molecular Biology High 24240613
2012 RNF8 ubiquitinates the p12 subunit of DNA polymerase δ (with UbcH5c as E2), targeting it for proteasomal degradation in response to DNA damage. RNF8 knockdown or knockout significantly reduces damage-induced p12 degradation. Biochemical purification from HeLa cells, proteomics identification, shRNA knockdown in human cells, RNF8(-/-) mouse epithelial cells Journal of Biological Chemistry Medium 23233665
2011 A single point mutation (I405A) in the RNF8 RING domain selectively disrupts interaction with UBCH8 and abolishes K48-linked polyubiquitylation but preserves interaction with UBC13 and K63-linked chain formation and downstream BRCA1/53BP1 assembly, revealing differential E2 utilization for distinct chain topologies. RNF8 I405A point mutant, in vitro ubiquitylation with linkage-specific analysis, co-immunoprecipitation with UBCH8/UBC13, immunofluorescence Nucleic Acids Research High 21911360
2016 RNF8 directly ubiquitinates Twist1 with K63-linked chains, promoting Twist1 nuclear localization and downstream EMT/cancer stem cell functions. K63-ubiquitination is required for Twist's transcriptional activities conferring chemoresistance. E3 ligase screen, co-immunoprecipitation, in vitro ubiquitylation, ubiquitin-linkage specific assays, nuclear localization assay, EMT/CSC functional readouts Molecular Cell High 27618486
2016 RNF8 E3 ligase stimulates Ubc13 polyubiquitination activity by modulating the conformation of ubiquitin covalently linked to the Ubc13 active site. Crystal structure of the RNF8-Ubc13~ubiquitin complex resolved, and separation-of-function mutations demonstrate that this stimulatory activity is essential for DSB signaling and independently required for BRCA1 recruitment. X-ray crystallography, SAXS, separation-of-function mutagenesis, in vitro ubiquitylation, immunofluorescence in cells Journal of Biological Chemistry High 26903517
2017 RNF8, together with the E2 Ube2S, assembles K11-linked ubiquitin chains on damaged chromatin including histone H2A/H2AX in an ATM-dependent manner. K11-linked ubiquitination regulates DNA damage-induced transcriptional silencing, distinct from K63-linked ubiquitination which recruits 53BP1 and BRCA1. K11 linkage-specific antibodies, in vitro ubiquitylation, Ube2S depletion, RNF8 depletion, transcription reporter assays Molecular Cell High 28525740
2017 EGF receptor activation leads to PKM2-mediated phosphorylation of histone H3 at T11; this phospho-H3 is bound by the RNF8 FHA domain, directing K48-linked polyubiquitylation of histone H3 at K4, causing H3 proteasomal degradation, nucleosome disassembly, and RNA Pol II access for MYC and CCND1 transcription. Co-immunoprecipitation, FHA domain-phosphopeptide binding, in vitro ubiquitylation, chromatin immunoprecipitation, nucleosome disassembly assay Journal of Experimental Medicine High 28507061
2017 RNF8 operates in the cytoplasm in post-mitotic cerebellar granule neurons (distinct from its nuclear role in dividing cells), where it interacts with HERC2 and NEURL4 scaffold to suppress synapse differentiation via UBC13-dependent ubiquitination. Neuronal-specific RNF8/UBC13 knockout increases parallel fiber synapses and impairs cerebellar-dependent learning. In vivo shRNA knockdown, conditional knockout in granule neurons, proteomic proximity analyses (BioID), immunofluorescence, electrophysiology, behavioral assays Nature Communications High 29097665
2018 L3MBTL2 is ubiquitylated by RNF8 following DNA damage, and ubiquitylated L3MBTL2 facilitates recruitment of RNF168 to DSBs, establishing L3MBTL2 as the missing link between RNF8 and RNF168 in the sequential ubiquitin signaling cascade. Co-immunoprecipitation, in vitro ubiquitylation, L3MBTL2 depletion, immunofluorescence, DSB repair assays Nature Cell Biology High 29581593
2019 The p97/VCP unfoldase and Ataxin-3 (ATX3) deubiquitinase form a complex with RNF8 to regulate its proteasome-dependent steady-state levels. Under genotoxic stress, p97-ATX3 promotes extraction of RNF8 from chromatin to balance DNA repair pathway choice. Co-immunoprecipitation, p97/ATX3 depletion, chromatin fractionation, proteasome inhibitor treatment, clonogenic survival EMBO Journal High 31613024
2019 RNF8 ubiquitinates NONO, targeting it for proteasomal degradation following UV-induced DNA damage. NONO degradation removes TOPBP1 chromatin loading, thus terminating ATR-CHK1 checkpoint signaling as a negative feedback loop. ATR is required for RNF8 recruitment to UV damage sites. Co-immunoprecipitation, in vitro ubiquitylation, NONO lysine mutants, CHK1 phosphorylation time course, clonogenic survival Nucleic Acids Research High 30445466
2018 RNF8 ubiquitylates the active NOTCH1 intracellular domain (N1ICD) with K48-linked chains, targeting it for proteasomal degradation, thereby acting as a negative regulator of Notch1 signaling and mammary luminal progenitor cell fate. Co-immunoprecipitation, in vitro ubiquitylation, Rnf8 knockout mouse mammary gland analysis, Notch reporter assay Journal of Clinical Investigation Medium 30222135
2007 RNF8 overexpression delays cytokinesis and causes aberrant mitotic figures in a ubiquitin-ligase-activity-dependent manner; RNF8 depletion delays exit from nocodazole-induced mitotic arrest associated with reduced cyclin B1 turnover, indicating RNF8 regulates the rate of mitotic exit. RNF8 overexpression and RING mutant expression, RNF8 depletion, time-lapse microscopy, cyclin B1 degradation assay Oncogene Medium 17724460
2004 RNF8 binds to RXRα through the N-terminal regions of both proteins and dose-dependently enhances RXRα-mediated transactivation in a RING-domain-dependent manner. The RING C403S point mutant or ΔN deletion of RNF8 abolished nuclear localization and transactivation enhancement. Yeast two-hybrid, pull-down, FRET in live cells, transient transfection reporter assay, RING point mutant Journal of Biological Chemistry Medium 14981089
2013 Human RNF8 (ortho-functional to yeast Dma proteins) localizes to centrosomes and cell division sites and promotes K63-linked ubiquitylation of the septin SEPT7. SEPT7 depletion increases cell division anomalies, analogous to yeast Dma-septin regulation. Immunofluorescence localization, in vitro ubiquitylation, SEPT7 depletion, yeast genetics Cell Cycle Medium 23442799
2012 RNF8-dependent ubiquitination of histone H2A during meiosis establishes H3K4 dimethylation (active epigenetic memory) on sex chromosomes, which persists through meiotic division. Subsequent RNF8-dependent modifications in spermatids include H3K4me3, histone crotonylation, and H2AFZ incorporation, enabling escape gene activation from silent sex chromosomes. Rnf8 knockout mouse model, ChIP-seq, chromatin conformation capture, immunofluorescence, RNA-seq Genes & Development High 23249736
2016 RNF8 ubiquitinates tankyrase 1 with K63-linked chains in late S/G2 phase, stabilizing tankyrase 1 and promoting its association with telomeres for sister telomere resolution. ABRO1/BRCC36 removes these chains in G1, timing cohesion resolution to the cell cycle. Co-immunoprecipitation, in vitro ubiquitylation, linkage-specific antibodies, cell cycle fractionation, telomere cohesion assay EMBO Journal High 27993934
2021 RNF8 directly ubiquitinates AKT via K63-linked chains, promoting AKT activation under physiological and genotoxic conditions, which contributes to lung cancer cell proliferation and chemotherapy resistance. Co-immunoprecipitation, in vitro ubiquitylation, K63 linkage-specific antibodies, RNF8 overexpression/knockdown with AKT activity readouts Cell Reports Medium 34686341
2017 RNF8 interacts with DYRK2 kinase; DYRK2 depletion impairs RNF8-mediated monoubiquitination of γH2AX and prevents 53BP1 foci formation at DSBs, indicating that DYRK2 facilitates RNF8-dependent DDR signaling. High-throughput screening, co-immunoprecipitation, γH2AX ubiquitination assay, DYRK2 knockdown, immunofluorescence, HR assay FEBS Letters Medium 28194753
2023 RNF8 ubiquitylates XRN2 to facilitate XRN2's recruitment to R-loop-prone genomic loci. In BRCA1-mutant cells, RNF8 deficiency reduces XRN2 occupancy at these sites, causing R-loop accumulation, replication-transcription collisions, and synthetic lethality. Co-immunoprecipitation, in vitro ubiquitylation, ChIP-seq for XRN2 and R-loop markers (S9.6 antibody), DRIP-seq, clonogenic survival Nucleic Acids Research High 37697435
2021 RNF8 ubiquitinates KMT5A (PR-Set7/SET8), promoting its recruitment to DSBs. RNF8-ubiquitinated KMT5A drives local H4K20me1 and enhances RNF168-catalyzed H2A ubiquitination; the interaction between the H2A acidic patch and KMT5A R188/R189 is critical for this function. Co-immunoprecipitation, in vitro ubiquitylation, KMT5A site-directed mutants, ChIP, H2A ubiquitination assay FASEB Journal Medium 33710666
2021 RNF8 ubiquitinates RecQL4 at K876, K1048, and K1101, promoting RecQL4's dissociation from DSB sites. Ubiquitination-defective RecQL4 is retained at DSBs and hinders recruitment of CtIP and Ku80 downstream. WRAP53β enhances the RecQL4-RNF8 association. Co-immunoprecipitation, in vitro ubiquitylation, site-directed RecQL4 mutants, laser microirradiation + live-cell imaging, WRAP53β knockdown Oncogenesis Medium 33674555
2017 HUWE1 primes histone H1 with ubiquitin following UV damage; RNF8 and Ubc13 then extend these modifications to K63-linked chains on H1. HUWE1 depletion reduces RNF168 and 53BP1 recruitment to UV damage sites while MDC1 (upstream of H1 ubiquitination) is unaffected. Di-Gly proteomics, HUWE1 depletion, RNF8/Ubc13 pathway assays, immunofluorescence foci assays Scientific Reports Medium 29127375
2012 RNF8 and BRCA1 localize to the nucleolus in the absence of DNA damage via RNF8 FHA domain interaction with ribosomal protein RPSA. Following γ-irradiation, RNF8 and BRCA1 translocate from the nucleolus to DSB foci; RPSA knockdown depletes nucleolar RNF8 and impairs bulk protein translation. Immunofluorescence co-localization, co-immunoprecipitation of RNF8 with RPSA, RPSA depletion, polysome profiling Experimental Cell Research Medium 22814251
2023 RNF8 interacts with MAD2 (closed conformer) via its RING domain, competing with p31comet, while CAMK2D (phospho-Thr287) serves as a molecular scaffold concentrating the RNF8-MAD2 complex via RNF8's FHA domain, thereby generating a mitotic checkpoint signal. RNF8 overexpression impairs mitotic progression in glioma stem cells in an FHA- and RING-dependent manner. Proximity proteomics, co-immunoprecipitation, CAMK2D phospho-mutants, FHA/RING domain mutants, live-cell mitosis imaging Cell Death & Differentiation Medium 37468549
2020 RNF8 promotes K63-linked ubiquitination of β-catenin, facilitating its nuclear translocation and subsequent c-Myc transcriptional activation in colon cancer cells. Co-immunoprecipitation, K63-specific ubiquitination assay, nuclear fractionation, RNF8 overexpression/knockdown with β-catenin/c-Myc readouts International Journal of Biological Sciences Low 32549753
2020 RNF8 promotes K63-linked ubiquitination of Slug, stabilizing Slug protein and activating PI3K/Akt signaling to promote EMT in lung cancer cells. Co-immunoprecipitation, K63-linked ubiquitination assay, Slug knockdown/rescue, PI3K inhibitor treatment, EMT marker analysis Molecular Cancer Research Low 32753472
2022 RNF8 ubiquitinates HDAC2, promoting its proteasomal degradation. In neurons, HDAC2 inhibits Reelin expression via H3K27me3 deacetylation; RNF8-mediated HDAC2 degradation de-represses Reelin, leading to GSK3β inhibition (via Ser9 phosphorylation) and neuronal protection against ischemic injury. Co-immunoprecipitation, ubiquitination assay, RNF8 knockdown, HDAC2 inhibitor, Reelin promoter ChIP, OGD/R neuronal model Molecular Neurobiology Low 35622272

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 835 18001825
2007 Orchestration of the DNA-damage response by the RNF8 ubiquitin ligase. Science (New York, N.Y.) 738 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 293 22373579
2010 RNF8-dependent histone modifications regulate nucleosome removal during spermatogenesis. Developmental cell 185 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 183 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 154 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 115 23615962
2012 DNA damage-inducible SUMOylation of HERC2 promotes RNF8 binding via a novel SUMO-binding Zinc finger. The Journal of cell biology 112 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 97 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 92 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 88 27618486
2018 L3MBTL2 orchestrates ubiquitin signalling by dictating the sequential recruitment of RNF8 and RNF168 after DNA damage. Nature cell biology 87 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 85 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
2008 RAP80 and RNF8, key players in the recruitment of repair proteins to DNA damage sites. Cancer letters 66 18550271
2017 DNA damage-induced histone H1 ubiquitylation is mediated by HUWE1 and stimulates the RNF8-RNF168 pathway. Scientific reports 65 29127375
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
2011 The E3 ubiquitin ligase Rnf8 stabilizes Tpp1 to promote telomere end protection. Nature structural & molecular biology 61 22101936
2009 The RNF8/RNF168 ubiquitin ligase cascade facilitates class switch recombination. Proceedings of the National Academy of Sciences of the United States of America 61 20080757
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
2011 Differential regulation of RNF8-mediated Lys48- and Lys63-based poly-ubiquitylation. Nucleic acids research 49 21911360
2019 The p97-Ataxin 3 complex regulates homeostasis of the DNA damage response E3 ubiquitin ligase RNF8. The EMBO journal 48 31613024
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 43 21444325
2018 Trabid inhibits hepatocellular carcinoma growth and metastasis by cleaving RNF8-induced K63 ubiquitination of Twist1. Cell death and differentiation 42 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/UBC13 ubiquitin signaling suppresses synapse formation in the mammalian brain. Nature communications 35 29097665
2017 RNF8 mediates histone H3 ubiquitylation and promotes glycolysis and tumorigenesis. The Journal of experimental medicine 34 28507061
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
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
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 33 23233665
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 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
2020 RNF8 induces β-catenin-mediated c-Myc expression and promotes colon cancer proliferation. International journal of biological sciences 28 32549753
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
2019 The Functions of DNA Damage Factor RNF8 in the Pathogenesis and Progression of Cancer. International journal of biological sciences 27 31182912
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.) 22 23442799
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
2012 RNF8 and RNF168 but not HERC2 are required for DNA damage-induced ubiquitylation in chicken DT40 cells. DNA repair 21 23010445
2023 RNF8 ubiquitylation of XRN2 facilitates R-loop resolution and restrains genomic instability in BRCA1 mutant cells. Nucleic acids research 20 37697435
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 15 32597970
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
2021 RNF8 ubiquitinates RecQL4 and promotes its dissociation from DNA double strand breaks. Oncogenesis 14 33674555
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
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
2020 RNF8 Dysregulation and Down-regulation During HTLV-1 Infection Promote Genomic Instability in Adult T-Cell Leukemia. PLoS pathogens 11 32453758
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 10 40055579
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
2023 CAMK2D serves as a molecular scaffold for RNF8-MAD2 complex to induce mitotic checkpoint in glioma. Cell death and differentiation 9 37468549
2021 Targeting RNF8 effectively reverses cisplatin and doxorubicin resistance in endometrial cancer. Biochemical and biophysical research communications 9 33548629
2021 The RNF8 and RNF168 Ubiquitin Ligases Regulate Pro- and Anti-Resection Activities at Broken DNA Ends During Non-Homologous End Joining. DNA repair 9 34481157