Affinage

RNF168

E3 ubiquitin-protein ligase RNF168 · UniProt Q8IYW5

Length
571 aa
Mass
65.0 kDa
Annotated
2026-04-28
100 papers in source corpus 57 papers cited in narrative 58 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

RNF168 is a RING-type E3 ubiquitin ligase that functions as a central amplifier of chromatin ubiquitin signals at DNA double-strand breaks, coordinating the recruitment of repair factors to dictate DSB repair pathway choice. Recruited downstream of RNF8 via ubiquitylated L3MBTL2 and K63-polyubiquitylated linker histone H1, RNF168 engages the nucleosome acidic patch through its RING domain and catalyzes site-specific monoubiquitination of H2A/H2AX at K13/K15 — marks read by 53BP1 and BARD1-BRCA1 to promote NHEJ and homologous recombination, respectively (PMID:22980979, PMID:30704900, PMID:39394267). Beyond histones, RNF168 ubiquitinates JMJD2A (freeing H4K20me2 for 53BP1 binding), 53BP1 itself (enabling its initial DSB recruitment), DHX9 (facilitating R-loop resolution), TOP2α, PARP1, and HDAC6, thereby integrating chromatin remodeling with DNA repair (PMID:22373579, PMID:24324146, PMID:33529165, PMID:27558965, PMID:37503842). RNF168 activity is tuned by a multi-layered regulatory code: K63-polyubiquitin-triggered liquid–liquid phase separation amplifies its catalytic output, while mTOR-S6K phosphorylation at S60 inhibits it, CDK1/2-PIN1-mediated SUMOylation at T208/K210 promotes p97-dependent removal from chromatin, SENP1 deSUMOylation prevents inhibitory LLPS, and USP7 stabilizes the protein by counteracting its own ubiquitin-dependent turnover (PMID:38968116, PMID:29403037, PMID:40229270, PMID:37350666, PMID:25894431).

Mechanistic history

Synthesis pass · year-by-year structured walk · 13 steps
  1. 2009 High

    The identity of the E3 ligase amplifying ubiquitin signals downstream of RNF8 at DSBs was unknown; discovery of RNF168 as a RING E3 that binds ubiquitin via MIU domains, assembles at DSBs in an RNF8-dependent manner, and amplifies K63-linked H2A/H2AX ubiquitination to thresholds required for 53BP1 and BRCA1 retention established RNF168 as the missing link in the DSB ubiquitin cascade.

    Evidence Co-IP, in vitro ubiquitin ligase assay, siRNA, MIU mutagenesis, and DDR foci in human cells

    PMID:19203579 PMID:19500350

    Open questions at the time
    • Precise histone target lysines not yet identified
    • Mechanism of nucleosome recognition unknown
    • In vivo chain-linkage specificity not fully mapped
  2. 2010 High

    RNF168 contains a previously uncharacterized ubiquitin-binding domain (UMI) whose integrity, together with MIU domains, is required for DSB localization and H2A ubiquitination, revealing the modular ubiquitin-reading architecture that drives RNF168 chromatin association.

    Evidence UBD mutagenesis, in vitro ubiquitin-binding, and DDR foci assays

    PMID:21041483

    Open questions at the time
    • Structural basis of UMI-ubiquitin interaction not resolved
    • Relative contributions of UMI vs MIU domains to recruitment not quantified
  3. 2012 High

    The specific histone target sites and chain linkages of RNF168 were established: RNF168 monoubiquitinates nucleosomal H2A at K13/K15 (not K118/K119), a site distinct from PRC1 marks, with K63-linked chains extended on this monoubiquitin; additionally, RNF168 ubiquitinates JMJD2A to free H4K20me2 for 53BP1 recognition, revealing a dual mechanism for 53BP1 recruitment.

    Evidence In vitro nucleosome ubiquitination, mass spectrometry, RING mutagenesis, histone mutagenesis, proteasome inhibitor experiments

    PMID:22373579 PMID:22713238 PMID:22980979

    Open questions at the time
    • Structural basis of K13/K15 selectivity unknown
    • Whether K27-linked chains contribute was not yet addressed
  4. 2013 High

    RNF168 was shown to ubiquitinate 53BP1 itself via K63-linked chains (required for 53BP1 DSB recruitment) and to partner with RAD6A/B E2 enzymes to ubiquitinate linker histone H1.2, broadening the substrate repertoire beyond core histones.

    Evidence Co-IP, E2 screen, in vitro ubiquitination, IRIF assays, checkpoint activation

    PMID:23525009 PMID:24324146

    Open questions at the time
    • Relative importance of 53BP1 ubiquitination vs. H2A ubiquitination for 53BP1 recruitment not resolved
    • Specific H1 sites targeted by RNF168 not mapped
  5. 2014 High

    The nucleosome acidic patch was identified as the critical docking site for RNF168 that directs ubiquitin transfer to K13/K15, explaining how RNF168 achieves substrate specificity on chromatin; separately, RNF168 was found to ubiquitinate TOP2α to regulate decatenation activity.

    Evidence In vitro nucleosome ubiquitination with acidic patch mutants, LANA peptide competition, Co-IP with TOP2α, decatenation assay

    PMID:24518117 PMID:24603765 PMID:27558965

    Open questions at the time
    • Atomic-resolution structure of RNF168–nucleosome complex not yet available
    • Functional interplay between NEDD8 and ubiquitin modifications on RNF168 not clarified
  6. 2015 High

    RNF168 was shown to catalyze noncanonical K27-linked ubiquitin chains on H2A/H2AX recognized by DDR mediators, and USP7 was identified as a stabilizer of RNF168 protein levels via deubiquitination, establishing both a new chain linkage and a key homeostatic regulator.

    Evidence Ubiquitin K27R mutagenesis, in vitro/in vivo ubiquitination, USP7 Co-IP and DUB assay, rescue experiments

    PMID:25578731 PMID:25894431

    Open questions at the time
    • Relative contribution of K27 vs K63 chains in vivo not quantified
    • Whether K27 chains form on K13/K15 monoubiquitin not shown
  7. 2017 High

    Crystal structures of RNF168 UDM1/UDM2 bound to K63-diubiquitin revealed that both domains fold as single α-helices achieving K63-linkage specificity by simultaneously contacting distal and proximal ubiquitin moieties, providing the first structural explanation for RNF168 recruitment selectivity.

    Evidence X-ray crystallography, mutagenesis, in vivo DSB foci assay

    PMID:29330428

    Open questions at the time
    • Full-length RNF168 structure not determined
    • How UDM engagement couples to RING-mediated catalysis unclear
  8. 2018 High

    Upstream recruitment of RNF168 was clarified: RNF8-ubiquitylated L3MBTL2 serves as the direct recruitment platform for RNF168 at DSBs; simultaneously, mTOR-S6K-mediated phosphorylation at S60 was identified as an inhibitory switch that reduces RNF168 E3 activity and stability, linking metabolic signaling to DNA repair capacity.

    Evidence Co-IP, in vitro ubiquitination, epistasis, kinase assay, S60A mutagenesis, mouse tumor model

    PMID:29403037 PMID:29581593

    Open questions at the time
    • Whether L3MBTL2 is the sole RNF168 recruiter or acts redundantly with other signals not fully tested
    • How S60 phosphorylation mechanistically impairs RING activity not structurally resolved
  9. 2019 High

    RNF168-generated monoubiquityl-H2A at K13/K15 was shown to directly recruit BARD1 via its BRCT-domain BUDR motif, establishing the molecular basis for BRCA1-PALB2-RAD51 assembly at DSBs and HR pathway choice; RNF168 also ubiquitinates DHX9 to promote R-loop resolution, revealing a function beyond canonical DSB repair.

    Evidence Mouse genetic epistasis, Co-IP, BRCT mutagenesis, HR foci assay, in vitro DHX9 ubiquitination, R-loop detection

    PMID:28240985 PMID:30704900 PMID:33529165 PMID:34408138

    Open questions at the time
    • Whether RNF168-DHX9 axis operates at all R-loops or specific loci not determined
    • Structural basis of BARD1-BUDR recognition of ubH2A not resolved at atomic level
  10. 2020 High

    RNF168 substrate specificity was extended to non-canonical H2A variants H2AZ and macroH2A1/2 at divergent N-terminal lysines, with the alpha1-extension helix identified as essential, broadening the chromatin landscape modified by RNF168.

    Evidence In vitro ubiquitination, histone variant mutagenesis, UMI mutagenesis, IRIF assay

    PMID:32424115

    Open questions at the time
    • Physiological significance of macroH2A ubiquitination at DSBs not established
    • Whether variant-specific ubiquitination differentially recruits repair factors unknown
  11. 2023 High

    SUMO modification was found to bifunctionally regulate RNF168: SUMOylation drives inhibitory LLPS that restricts RNF168 at DSBs, counteracted by SENP1-mediated deSUMOylation; separately, RNF168 ubiquitinates HDAC6 at K116 for proteasomal degradation, removing a competitive blocker of H2A interaction.

    Evidence Phase separation assays in vitro/in vivo, SUMO modification assay, SENP1 Co-IP, HDAC6 K116 mutagenesis, NHEJ repair assay

    PMID:37350666 PMID:37503842

    Open questions at the time
    • Whether SENP1-mediated deSUMOylation is cell-cycle regulated not shown
    • How HDAC6 degradation kinetics relate to repair factor recruitment timing unknown
  12. 2024 High

    Cryo-EM structures captured RNF168 on the nucleosome in a unique 'helix-anchoring' mode, resolving the complete catalytic cycle including transient K13 and K15 monoubiquitination and dual-site modification; K63-polyubiquitylated linker histone H1 was shown to directly stimulate RNF168 activity by enhancing its chromatosome affinity, and K63-ubiquitin-triggered LLPS via an IDR amplifies H2AX ubiquitination in a positive feedback loop; a PCNA-binding DPIP motif was found to recruit RNF168 to replication factories independently of the DSB pathway.

    Evidence Cryo-EM, NMR, chemical ubiquitin ligation, in vitro phase separation, DNA fiber assays, domain mutagenesis

    PMID:38242129 PMID:38968116 PMID:39363740 PMID:39394267 PMID:39445802

    Open questions at the time
    • Whether LLPS condensates form at endogenous DSBs in living cells with physiological RNF168 levels not confirmed
    • Functional consequence of dual K13+K15 monoubiquitination versus single-site modification in repair pathway choice not tested
    • Role of PCNA-dependent RNF168 at replication forks in replication stress response not fully characterized
  13. 2025 High

    A CDK1/2-PIN1-SUMO2 cascade was identified that limits RNF168 accumulation: CDK phosphorylation at T208 triggers PIN1 binding, which promotes SUMO2 modification at K210 and subsequent p97/VCP-mediated removal from chromatin; ZNF451-catalyzed SUMO2 modification was separately shown to stabilize RNF168, revealing opposing SUMOylation circuits controlling RNF168 homeostasis at DSBs.

    Evidence Phosphorylation/SUMOylation assays, T208/K210 mutagenesis, p97 inhibitor, IRIF assays, epistasis

    PMID:40055579 PMID:40229270

    Open questions at the time
    • How cells distinguish stabilizing (ZNF451) vs. removal-promoting (PIN1-p97) SUMO2 modifications on the same protein not mechanistically resolved
    • Whether the CDK-PIN1 axis is active only in specific cell-cycle phases not determined

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key open questions remain: (1) how the multiple PTM inputs (phosphorylation, SUMOylation, neddylation, PARylation) are integrated in real time at a single DSB to tune RNF168 residence and catalytic output; (2) the structural basis of RNF168 LLPS condensates at endogenous damage sites; (3) the physiological significance of RNF168's replication-fork function via PCNA; and (4) whether RNF168 non-histone substrates (DHX9, TOP2α, PARP1, HDAC6) are ubiquitinated within the same chromatin condensate or via distinct mechanisms.
  • Integrated quantitative model of RNF168 regulation at individual DSBs lacking
  • In vivo LLPS condensate dynamics at physiological expression levels not imaged
  • PCNA-dependent replication function poorly separated from DSB function in animal models

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140096 catalytic activity, acting on a protein 10 GO:0016740 transferase activity 5 GO:0016874 ligase activity 5 GO:0042393 histone binding 5
Localization
GO:0005694 chromosome 6 GO:0005634 nucleus 4
Pathway
R-HSA-73894 DNA Repair 8 R-HSA-4839726 Chromatin organization 5 R-HSA-162582 Signal Transduction 2 R-HSA-69306 DNA Replication 1
Partners
53BP1DHX9L3MBTL2PALB2PCNAPIN1RNF8USP7

Evidence

Reading pass · 58 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2009 RNF168 is a chromatin-associated RING finger E3 ubiquitin ligase that binds ubiquitin via MIU domains, assembles at DSBs in an RNF8-dependent manner, and amplifies K63-linked ubiquitin conjugates on H2A and H2AX to the threshold required for retention of 53BP1 and BRCA1 at damage sites. Co-IP, in vitro ubiquitin ligase assay, siRNA knockdown, immunofluorescence at DSB foci, MIU domain mutagenesis Cell High 19203579
2009 RNF168 ubiquitinates histones H2A and H2AX but not H2B, forming K63-linked polyubiquitin chains both in vitro and in vivo; MIU domain inactivation impairs ubiquitin binding and chromatin association in vivo. In vitro ubiquitin ligase assay, in vivo ubiquitination, MIU mutagenesis, immunofluorescence BMC molecular biology High 19500350
2012 RNF168, but not RNF8, catalyzes monoubiquitination of nucleosomal H2A/H2AX specifically at K13-15; RNF8 is inactive toward nucleosomal H2A; structure-based mutagenesis of the RING domain identified a charged residue determining nucleosomal substrate recognition; K63-linked chains are conjugated to the RNF168-dependent K13-15 monoubiquitin mark, not K118-119. In vitro nucleosome ubiquitination assay, RING domain mutagenesis, mass spectrometry, structure-based analysis Cell High 22980979
2012 RNF168 (and RNF8) ubiquitinate KDM4A/JMJD2A, targeting it for proteasomal degradation after DNA damage, thereby freeing H4K20me2 for 53BP1 binding; ectopic JMJD2A blocks 53BP1 recruitment to DSBs. In vitro ubiquitination assay, co-IP, proteasome inhibitor treatment, knockdown rescue experiment, 53BP1 foci assay The EMBO journal High 22373579
2012 RNF168 generates a novel ubiquitin mark at the N-terminal tail of histone H2A at K13 and K15; histone mutants lacking K13/K15 impair RNF168-dependent ubiquitination; this site is distinct from the canonical C-terminal K118/K119 site. Histone mutagenesis, in vivo ubiquitination assay, mass spectrometry Cell cycle High 22713238
2010 RNF168 contains a novel ubiquitin-binding domain called UMI (UIM- and MIU-related UBD) centered on two leucine residues; integrity of the UMI plus both MIUs is required for proper RNF168 localization to DDR foci and for H2A ubiquitination and 53BP1 recruitment. UBD mutagenesis, in vitro ubiquitin-binding assay, immunofluorescence at DDR foci Molecular and cellular biology High 21041483
2015 RNF168 promotes noncanonical K27-linked ubiquitination both in vivo and in vitro; K27 of ubiquitin is required for RNF168-dependent chromatin ubiquitination of H2A/H2AX and is directly recognized by DDR mediators 53BP1, RAP80, RNF168, and RNF169. In vitro ubiquitination assay, ubiquitin mutant analysis, co-IP, DDR foci assay Cell reports High 25578731
2013 RNF168 mediates K63-linked ubiquitylation of 53BP1, which is required for the initial recruitment of 53BP1 to DSB sites and for its functions in DNA damage repair, checkpoint activation, and genomic integrity. Co-IP, K63-ubiquitin chain analysis, 53BP1 IRIF assay, checkpoint activation assay, genome integrity readout Proceedings of the National Academy of Sciences of the United States of America High 24324146
2014 The nucleosome acidic patch is required for RNF168-dependent H2A/H2AX ubiquitination; nucleosomes containing a mutated acidic patch show defective H2A ubiquitination by RNF168 in vitro; the acidic patch acts as substrate to enhance E3-mediated ubiquitin discharge from E2 and redirect ubiquitination to K13-15. In vitro nucleosome ubiquitination assay, acidic patch mutagenesis, in vivo DDR foci assay with LANA peptide Nature communications High 24518117
2014 The nucleosome acidic patch is required for RNF168- and RING1B/BMI1-dependent H2A/H2AX ubiquitination in vivo; perturbation of the acidic patch by a viral LANA peptide results in defective H2AX ubiquitination and impaired RNF168-dependent 53BP1 and BRCA1 recruitment. Nucleosome acidic patch mutagenesis, in vitro ubiquitination assay, in vivo DDR foci assay PLoS genetics High 24603765
2017 RNF169 bridges ubiquitin and histone surfaces via a three-pronged interaction (canonical ubiquitin-binding helix plus two arginine-rich motifs contacting the nucleosome acidic patch), stabilizing a pre-existing ubiquitin orientation on RNF168-ubiquitinated NCP to displace 53BP1; RAD18 binds NCP-ubme through a UBD contacting ubiquitin and nucleosome surfaces accessed by 53BP1. NMR spectroscopy, biochemical binding assays, displacement assays Molecular cell High 28506460
2017 RNF168 directly interacts with PALB2 via a newly identified PALB2-interacting domain (PID) in RNF168 and the WD40 domain of PALB2; this interaction recruits PALB2-containing HR complexes to DSBs in S/G2 cells, coupling PALB2-dependent homologous recombination to H2A ubiquitylation. Co-IP, domain mapping, epistasis by siRNA knockdown, HR repair assay eLife High 28240985
2018 L3MBTL2 is ubiquitylated by RNF8 and serves as the missing link that recruits RNF168 to DSBs; ubiquitylated L3MBTL2 facilitates RNF168 recruitment and promotes DSB repair. Co-IP, in vitro ubiquitination, siRNA knockdown, DDR foci assay, epistasis Nature cell biology High 29581593
2018 The mTOR-S6K pathway phosphorylates RNF168 at Ser60, inhibiting its E3 ligase activity, accelerating its proteolysis, and impairing its function in the DNA damage response; loss of LKB1 hyperactivates mTORC1-S6K signaling and decreases RNF168 expression; phospho-deficient RNF168-S60A rescues DDR defects and suppresses tumorigenesis caused by Lkb1 loss. Phosphorylation assay, in vitro E3 ligase assay, mutagenesis (S60A), mouse tumor model, Western blot Nature cell biology High 29403037
2019 RNF168, in addition to its canonical role in inhibiting end resection, acts redundantly with BRCA1 to load PALB2 onto damaged DNA; RNF168-generated mUb-H2A recruits BARD1 through a BRCT domain BUDR motif, and BARD1-BRCA1 subsequently accumulates PALB2-RAD51 at DSBs. Mouse genetics (epistasis), co-IP, PALB2-RAD51 foci assay, forced targeting of PALB2 Molecular cell High 30704900
2019 RNF168 directly ubiquitylates DHX9 helicase to facilitate its recruitment to R-loop-prone genomic loci; RNF168 deficiency impairs DHX9 recruitment and R-loop resolution, leading to R-loop accumulation, DSBs, and senescence in BRCA1/2-mutant cells. Interactome assays, in vitro ubiquitination, siRNA knockdown, R-loop detection, DSB assay The Journal of clinical investigation High 33529165
2019 RNF168-generated mUb-H2A recruits BARD1 via a BRCT domain ubiquitin-dependent recruitment motif (BUDR); subsequently BARD1-BRCA1 accumulate PALB2-RAD51 at DNA breaks via the coiled-coil domain-mediated BRCA1-PALB2 interaction. Co-IP, BRCT domain mutagenesis, HR foci assay, mouse genetics Nature communications High 34408138
2019 The crystal structures of RNF168 UDM1 and UDM2 bound to K63-linked diubiquitin reveal that both domains fold as single α-helices and achieve specificity for K63-linked chains by simultaneously binding distal and proximal Ub moieties; mutations in UDM2 Ub-interacting residues prevent RNF168 accumulation at DSB sites. X-ray crystallography, mutagenesis, in vivo DSB foci accumulation assay Nature communications High 29330428
2019 NMR spectroscopy and crosslinking mass spectrometry show that RNF168 binds the acidic patch on the nucleosome surface via its RING domain, directing the E2 to the K13/K15 target lysines to achieve ubiquitination site specificity. NMR spectroscopy, crosslinking mass spectrometry, mutagenesis, data-driven structural modelling Nature communications High 30988309
2010 The viral E3 ligase ICP0 of herpes simplex virus type 1 targets RNF8 and RNF168 for proteasomal degradation, resulting in loss of ubiquitinated H2A forms and mobilization of DNA repair proteins, demonstrating that RNF168 is essential for anchoring repair factors at DSBs. Viral infection, Western blot for protein degradation, ubiquitinated H2A assay, repair factor foci assay The EMBO journal High 20075863
2012 SMARCA5/SNF2H interacts with RNF168 in a DNA damage- and PARP-dependent manner; RNF168 becomes poly(ADP-ribosyl)ated after DNA damage; SMARCA5 promotes RNF168 accumulation at DSBs and subsequent ubiquitin conjugation; PARP selectively promotes spreading of SMARCA5 and RNF168-driven ubiquitin response. Co-IP, PARP inhibitor treatment, siRNA knockdown, IRIF assay, PARP activity assay Journal of cell science High 23264744
2013 USP44 counteracts RNF8/RNF168-mediated ubiquitin signaling at DSBs by deubiquitinating H2A and inhibiting RNF168 accrual; USP44 is recruited to RNF168-generated ubiquitylation products at DSB sites. DUB overexpression screen, H2A deubiquitination assay, IRIF assay The Journal of biological chemistry High 23615962
2013 USP3 deubiquitinates H2A and γH2AX at K13 and K15 (the RNF168 target sites) in response to DNA damage; USP3 overexpression abrogates ubiquitin-conjugate foci and impairs BRCA1 and 53BP1 accumulation at damage sites. Deubiquitination assay, mutagenesis of H2A K13/K15, IRIF assay, siRNA knockdown Cell cycle High 24196443
2013 RNF168 forms a functional complex with RAD6A/RAD6B E2 enzymes; this complex targets histone H1.2 for ubiquitination in vitro and regulates DNA damage-induced H1.2 ubiquitination in vivo; loss of RAD6 reduces DNA damage-induced ubiquitination and impairs BRCA1/53BP1 foci. E2 screen, Co-IP, in vitro ubiquitination assay, IRIF assay, siRNA knockdown Journal of cell science High 23525009
2014 RNF168 interacts with TOP2α and mediates its ubiquitylation; RNF168 deficiency impairs decatenation activity of TOP2α, promotes mitotic abnormalities, and confers resistance to etoposide; USP10 antagonizes RNF168 by deubiquitylating TOP2α. Co-IP, in vitro ubiquitination, decatenation assay, siRNA knockdown, mitotic abnormality assay Nature communications High 27558965
2014 RNF168-mediated H2A neddylation antagonizes H2A ubiquitylation; RNF168 itself is a substrate for NEDD8, and neddylation of RNF168 is necessary for its E3 ubiquitin activity by enabling its interaction with the E2 enzyme Ubc13. In vitro neddylation and ubiquitination assay, Co-IP, NEDD8 pathway inhibition, siRNA knockdown Journal of cell science Medium 24634510
2015 USP7 physically binds RNF168 in vitro and in vivo, deubiquitinates RNF168, and stabilizes it; USP7 disruption reduces H2A ubiquitination and impairs BRCA1 and 53BP1 foci formation; ectopic RNF168 expression rescues DDR defects in USP7-disrupted cells. Co-IP, in vitro binding assay, deubiquitination assay, IRIF assay, rescue experiment Cell cycle High 25894431
2015 RNF168-dependent recruitment of LSD1 to DSBs promotes local H3K4me2 demethylation and H2A/H2AX ubiquitination; CK2-mediated phosphorylation of LSD1 at S131/S137 promotes its interaction with RNF168 and RNF168-dependent 53BP1 ubiquitination and recruitment; WIP1 dephosphorylates LSD1 to counteract this. Co-IP, kinase assay, phosphorylation-defective mutant analysis, 53BP1 foci assay Nucleic acids research Medium 25999347
2016 RNF168 cooperates with RNF8 to ubiquitinate SUMOylated FOXM1 with K48-linked polyubiquitin chains, leading to its degradation; RNF8 recruits RNF168 to FOXM1 upon epirubicin treatment; SUMOylation of FOXM1 is required for RNF168 recruitment. Co-IP, ubiquitination assay with chain-linkage analysis, cycloheximide chase, FOXM1-5x(K>R) mutant Oncogenesis Medium 27526106
2017 DNA damage-induced histone H1 ubiquitylation by HUWE1 is required for subsequent RNF8-dependent K63-linked chain extension on H1, which in turn stimulates RNF168 recruitment to damage sites; HUWE1 depletion reduces RNF168 and 53BP1 foci. di-Gly proteomics, siRNA knockdown, IRIF assay, epistasis analysis Scientific reports Medium 29127375
2018 RNF168 ubiquitinates PARP1 via K48-linked chains, accelerating PARP1 degradation in the presence of PAR chains; PAR chains and RNF168's E3 ligase activity are both required for proper HR/NHEJ balance, as established by mutants lacking E3 or PAR-binding activity. Co-IP, mass spectrometry, in vitro ubiquitination assay, micro-irradiation accumulation assay, comet assay Molecules and cells Medium 30037213
2018 USP14 directly interacts with RNF168 via the MIU1 domain of RNF168, antagonizes RNF168-dependent ubiquitination of H2A and 53BP1 IRIF formation; USP14 is a substrate of autophagy via SQSTM1; loss of autophagy increases USP14 activity and impairs RNF168-dependent DDR. Co-IP with domain mapping (MIU1), DUB activity assay, siRNA knockdown, IRIF assay Autophagy Medium 29995557
2019 HPV E7 oncoprotein binds directly to a new regulatory domain of RNF168 without affecting its enzymatic activity, subverting its function at DSBs and promoting homology-directed recombination; RNF168 knockdown impairs viral genome amplification in differentiated keratinocytes. Direct binding assay, in vitro E3 ligase activity assay, IRIF assay, HPV genome amplification assay Proceedings of the National Academy of Sciences of the United States of America Medium 31501315
2019 PRMT5 sustains RNF168 expression; suppression of PRMT5 (in MTAP-deficient cells) attenuates RNF168, leading to H2AX destabilization by SMURF2; RNF168 and SMURF2 serve as a stabilizer and destabilizer of H2AX, respectively, via their dynamic interactions with H2AX. Western blot, siRNA knockdown, co-IP, H2AX stability assay Cell reports Medium 31533041
2020 RNF168 ubiquitinates non-canonical H2A variants H2AZ and macroH2A1/2 at divergent N-terminal tail lysines; the positively charged alpha1-extension helix is essential for RNF168-mediated ubiquitination; mutation of RNF168 UMI hydrophilic acidic residues abolishes ubiquitination and 53BP1/BRCA1 IRIF formation. In vitro ubiquitination assay, histone variant mutagenesis, UMI domain mutagenesis, IRIF assay Nature communications High 32424115
2021 RNF168 interacts with DHX9 helicase and directly ubiquitylates it to facilitate DHX9 recruitment to R-loop-prone loci; loss of RNF168 impairs DHX9 function in R-loop resolution. Interactome/Co-IP assay, in vitro ubiquitination, R-loop immunofluorescence, siRNA knockdown The Journal of clinical investigation High 33529165
2021 RNF168 is epistatic with SLX4 in promoting MMC tolerance; RNF168 is required for mitomycin C-induced SLX4 foci formation and accumulation of SLX4 at ICL damage sites, establishing RNF168 as a critical E3 ligase in the ubiquitin signal transduction for Fanconi anemia pathway ICL repair. siRNA screen, IRIF assay, laser-ICL track accumulation, epistasis analysis Cell reports Medium 34706224
2021 KMT5A is ubiquitinated by RNF8 in vitro and in vivo; RNF8-induced KMT5A ubiquitination increases its binding to RNF168; KMT5A interaction with the H2A acidic patch (via R188/R189) promotes RNF168's catalytic activity toward H2A; KMT5A links H4K20 monomethylation to H2A ubiquitination at DSBs. In vitro ubiquitination assay, Co-IP, acidic patch mutagenesis, H2A ubiquitination assay FASEB journal Medium 33710666
2023 SUMOylated RNF168 undergoes liquid-liquid phase separation (LLPS), restricting its recruitment to DNA damage sites and reducing H2A ubiquitination; SENP1 acts as a specific deSUMOylase for RNF168, promoting deSUMOylation to prevent LLPS and enable RNF168 function at DSBs. SUMO modification assay, phase separation assay in vitro and in vivo, SENP1 Co-IP, H2A ubiquitination assay, NHEJ repair assay Cancer research High 37350666
2023 HDAC6 interacts with H2A/H2AX to prevent its interaction with RNF168 in unstressed cells; upon DSBs, RNF168 ubiquitinates HDAC6 at K116, leading to its proteasomal degradation and enabling RNF168-H2A/H2AX interaction and H2A ubiquitination for DSB repair. Co-IP, in vitro ubiquitination, proteasome inhibition, site-directed mutagenesis (K116), repair factor foci assay Nucleic acids research High 37503842
2024 Cryo-EM structures of RNF168-UbcH5c~Ub-nucleosome complex reveal a 'helix-anchoring' mode for RNF168 on the nucleosome, distinct from dimeric E3 ligases; structures capture transient H2A K13 and K15 monoubiquitination and adjacent dual monoubiquitination reactions. Cryo-EM structural determination, chemical ubiquitin ligation strategies, functional ubiquitination assay Nature chemical biology High 39394267
2024 Cryo-EM and NMR reveal the complete reaction cycle of RNF168 on the nucleosome; a canonical ubiquitin-binding domain within full-length RNF168 engages both ubiquitin and the nucleosome surface, driving a signal amplification loop; this interaction clarifies how site-specific ubiquitin recognition propels H2A ubiquitin chain accumulation at DSBs. Cryo-EM, NMR spectroscopy, functional ubiquitination assay, mutagenesis Molecular cell High 38242129
2024 K63-linked polyubiquitylated linker histone H1 directly stimulates RNF168 nucleosomal H2A ubiquitylation activity by enhancing RNF168 affinity to the chromatosome; UDM1 of RNF168 binds K63-linked ubiquitin chain on H1.0; H1K17Ub2 shows strongest RNF168 activation. Chemical synthesis of ubiquitylated H1 variants, in vitro ubiquitination assay, cryo-EM, biochemical affinity measurement Angewandte Chemie High 39363740
2024 RNF168 is recruited to DNA replication factories via a degenerate PCNA-interacting peptide (DPIP) motif in its C-terminus and its MIU1 domain, mediating binding to mono-ubiquitylated PCNA; this recruitment is independent of the canonical ATM-RNF8 DSB response pathway; RNF168 promotes ongoing DNA replication via this PCNA-dependent mechanism. Domain mutagenesis (DPIP/MIU1), co-IP with PCNA, replication factory localization, DNA fiber assay, 53BP1 IRIF assay for separation of functions Nucleic acids research High 39445802
2024 K63-linked polyubiquitin chains trigger RNF168 liquid-liquid phase separation (LLPS) via an intrinsically disordered region (aa 460-550); LLPS enhances RNF168-mediated H2A.X ubiquitination in a positive feedback loop; LLPS deficiency impairs 53BP1 and BRCA1 recruitment and DSB repair. In vitro phase separation assay with purified RNF168, in vivo condensate imaging, domain mapping, H2AX ubiquitination assay, DSB repair assay Proceedings of the National Academy of Sciences of the United States of America High 38968116
2025 CDK1/2 phosphorylates RNF168 at threonine-208, inducing interaction with the peptidyl-prolyl isomerase PIN1; PIN1 promotes RNF168 SUMOylation at K210, resulting in p97/VCP-mediated removal of RNF168 from damaged chromatin; this PIN1-SUMO2/3 motif (SPaCR) limits excessive RNF168 accumulation and ubiquitin signaling. Phosphorylation assay, Co-IP, SUMOylation assay, mutagenesis (T208/K210), p97 inhibitor, IRIF assay Nature communications High 40229270
2025 ZNF451 catalyzes SUMO2 modification of RNF168, stabilizing RNF168 and enhancing its accumulation at DSB sites; ZNF451 and RNF8 jointly regulate RNF168 in a competitive/cooperative manner; loss of both ZNF451 and RNF8 markedly impedes RNF168 recruitment. Co-IP, SUMOylation assay, IRIF assay, siRNA knockdown, epistasis analysis Cell death and differentiation Medium 40055579
2024 UBE2D3 contributes to RNF168-mediated chromatin ubiquitination and 53BP1 recruitment at DSBs; simultaneously UBE2D3 limits RNF168 accumulation to facilitate ATM-mediated KAP1-S824 phosphorylation and NHEJ; RNF168 hyperaccumulation upon UBE2D3 loss causes aberrant PP2A activity that restricts KAP1 phosphorylation. siRNA knockdown, telomere NHEJ assay, IRIF assay, phosphorylation assay, epistasis analysis Nature communications Medium 38866770
2015 RNF168 partially localizes to PML nuclear bodies through its UMI/MIU1 ubiquitin-interacting region; RNF168 associates with SUMO2/3-modified proteins via its ubiquitin-binding sequences; RNF168 preferentially binds hybrid SUMO2-K63 ubiquitin chains over K63-ubiquitin chains or SUMO2 alone in vitro; overexpression of RNF168 induces loss of PML nuclear bodies. shRNA screen, immunofluorescence localization, in vitro chain-binding assay, co-IP Journal of cell science Medium 26675234
2009 The RNF8/RNF168 ubiquitination cascade facilitates B cell class switch recombination (CSR); knockdown of RNF168 or 53BP1 reduces CSR efficiency, while RNF8/RNF168 deficiency does not protect cells from Nutlin-3-mediated apoptosis (unlike 53BP1 deficiency), indicating separable functions. siRNA knockdown, CSR assay (IgA switching), Nutlin-3 apoptosis assay Proceedings of the National Academy of Sciences of the United States of America Medium 20080757
2012 Structural analysis shows RNF168 RING domain adopts a C3HC4 cross-brace fold but, unlike RNF8, does not stably associate with UBC13 in vitro or in vivo; RING domains of RNF8 and RNF168 are not functionally interchangeable in domain-swap experiments. X-ray crystallography (RING domain), co-IP, in vitro binding assay, domain-swap experiment Cell cycle Medium 23255131
2021 MRE11 and UBR5 cooperate to suppress RNF168 accumulation at dysfunctional telomeres; MRE11 limits RNF168 recruitment via BRCC3-mediated deubiquitination of γH2AX; UBR5 directly ubiquitinates and destroys RNF168 at telomeres; combined loss of MRE11 and UBR5 leads to RNF168/53BP1 telomeric accumulation and chromosome fusion reversed by RNF168 suppression. siRNA knockdown, co-IP, telomere FISH for fusion, 53BP1/RNF168 telomeric foci assay, epistasis Frontiers in oncology Medium 34881184
2018 RNF168 stabilizes STAT1 protein by associating with it in the nucleus and inhibiting its poly-ubiquitination and degradation, thereby sustaining JAK-STAT signaling in esophageal cancer cells. Co-IP, ubiquitination assay, Western blot for protein stability, siRNA knockdown Journal of cellular and molecular medicine Low 30506884
2021 RNF168 directly interacts with RhoC and promotes its ubiquitination and proteasomal degradation in non-small cell lung cancer cells; RNF168-mediated RhoC degradation suppresses cancer stem cell-like traits. Co-IP, ubiquitination assay, Western blot for protein stability, overexpression/knockdown functional assay Environmental toxicology Low 34873829
2018 RNF126 directly interacts with and ubiquitinates RNF168; overexpression of catalytically active (but not inactive) RNF126 diminishes H2AX ubiquitination, FK2, 53BP1, and RAP80 foci; RNF126 is recruited to UV laser damage in an RNF8-dependent manner. Co-IP, in vitro ubiquitination assay, catalytic mutant analysis, IRIF assay Genomics, proteomics & bioinformatics Medium 30529286
2023 Compound 5a (quinazoline-triazole derivative) directly binds both SQSTM1/P62 and RNF168, promoting their interaction, decreasing RNF168-mediated H2A ubiquitination, and compromising HR-mediated DNA repair. Target profiling/binding assay, H2A ubiquitination assay, HR repair assay, xenograft tumor model Journal of medicinal chemistry Low 36331508
2017 NIPBL (cohesin loading factor) recruitment to DSBs requires RNF168 (and MDC1 and HP1γ); NIPBL accumulation at damage sites is mediated by its C-terminal HEAT repeat/HP1-interacting region. siRNA knockdown of RNF168, micro-irradiation IRIF assay, domain mapping Biochemical and biophysical research communications Medium 21784059
2019 Cadmium directly binds to RNF168, induces its ubiquitin-proteasome-dependent degradation, and suppresses RNF168 ubiquitin-ligase activity in vitro, thereby disrupting DSB signaling and impairing 53BP1/BRCA1 recruitment. Direct binding assay, in vitro E3 ligase activity assay, proteasome inhibitor rescue, IRIF assay Food and chemical toxicology Medium 31376412

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2009 RNF168 binds and amplifies ubiquitin conjugates on damaged chromosomes to allow accumulation of repair proteins. Cell 757 19203579
2012 RNF168 ubiquitinates K13-15 on H2A/H2AX to drive DNA damage signaling. Cell 539 22980979
2012 RNF8- and RNF168-dependent degradation of KDM4A/JMJD2A triggers 53BP1 recruitment to DNA damage sites. The EMBO journal 293 22373579
2015 RNF168 promotes noncanonical K27 ubiquitination to signal DNA damage. Cell reports 164 25578731
2010 A viral E3 ligase targets RNF8 and RNF168 to control histone ubiquitination and DNA damage responses. The EMBO journal 151 20075863
2012 A novel ubiquitin mark at the N-terminal tail of histone H2As targeted by RNF168 ubiquitin ligase. Cell cycle (Georgetown, Tex.) 142 22713238
2012 Poly(ADP-ribosyl)ation links the chromatin remodeler SMARCA5/SNF2H to RNF168-dependent DNA damage signaling. Journal of cell science 119 23264744
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
2009 RNF168, a new RING finger, MIU-containing protein that modifies chromatin by ubiquitination of histones H2A and H2AX. BMC molecular biology 109 19500350
2018 The mTOR-S6K pathway links growth signalling to DNA damage response by targeting RNF168. Nature cell biology 107 29403037
2013 USP3 counteracts RNF168 via deubiquitinating H2A and γH2AX at lysine 13 and 15. Cell cycle (Georgetown, Tex.) 99 24196443
2019 BRCA1 Haploinsufficiency Is Masked by RNF168-Mediated Chromatin Ubiquitylation. Molecular cell 95 30704900
2018 L3MBTL2 orchestrates ubiquitin signalling by dictating the sequential recruitment of RNF8 and RNF168 after DNA damage. Nature cell biology 87 29581593
2013 RNF168 ubiquitylates 53BP1 and controls its response to DNA double-strand breaks. Proceedings of the National Academy of Sciences of the United States of America 85 24324146
2014 Nucleosome acidic patch promotes RNF168- and RING1B/BMI1-dependent H2AX and H2A ubiquitination and DNA damage signaling. PLoS genetics 82 24603765
2014 The nucleosome acidic patch plays a critical role in RNF168-dependent ubiquitination of histone H2A. Nature communications 81 24518117
2017 Mechanisms of Ubiquitin-Nucleosome Recognition and Regulation of 53BP1 Chromatin Recruitment by RNF168/169 and RAD18. Molecular cell 76 28506460
2023 SENP1 Decreases RNF168 Phase Separation to Promote DNA Damage Repair and Drug Resistance in Colon Cancer. Cancer research 75 37350666
2015 USP7 deubiquitinase promotes ubiquitin-dependent DNA damage signaling by stabilizing RNF168. Cell cycle (Georgetown, Tex.) 72 25894431
2017 A PALB2-interacting domain in RNF168 couples homologous recombination to DNA break-induced chromatin ubiquitylation. eLife 71 28240985
2018 USP14 regulates DNA damage repair by targeting RNF168-dependent ubiquitination. Autophagy 70 29995557
2017 DNA damage-induced histone H1 ubiquitylation is mediated by HUWE1 and stimulates the RNF8-RNF168 pathway. Scientific reports 65 29127375
2011 Homozygous deficiency of ubiquitin-ligase ring-finger protein RNF168 mimics the radiosensitivity syndrome of ataxia-telangiectasia. Cell death and differentiation 65 21394101
2015 Modulation of LSD1 phosphorylation by CK2/WIP1 regulates RNF168-dependent 53BP1 recruitment in response to DNA damage. Nucleic acids research 63 25999347
2021 RNF168 regulates R-loop resolution and genomic stability in BRCA1/2-deficient tumors. The Journal of clinical investigation 62 33529165
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
2010 UMI, a novel RNF168 ubiquitin binding domain involved in the DNA damage signaling pathway. Molecular and cellular biology 60 21041483
2019 Human papillomavirus E7 oncoprotein targets RNF168 to hijack the host DNA damage response. Proceedings of the National Academy of Sciences of the United States of America 59 31501315
2014 RNF168-mediated H2A neddylation antagonizes ubiquitylation of H2A and regulates DNA damage repair. Journal of cell science 59 24634510
2015 USP11 Is a Negative Regulator to γH2AX Ubiquitylation by RNF8/RNF168. The Journal of biological chemistry 57 26507658
2021 RNF168-mediated localization of BARD1 recruits the BRCA1-PALB2 complex to DNA damage. Nature communications 55 34408138
2019 Structural basis of specific H2A K13/K15 ubiquitination by RNF168. Nature communications 48 30988309
2017 The RNF168 paralog RNF169 defines a new class of ubiquitylated histone reader involved in the response to DNA damage. eLife 48 28406400
2016 RNF168 and USP10 regulate topoisomerase IIα function via opposing effects on its ubiquitylation. Nature communications 47 27558965
2012 RING finger nuclear factor RNF168 is important for defects in homologous recombination caused by loss of the breast cancer susceptibility factor BRCA1. The Journal of biological chemistry 44 23055523
2016 Tumors overexpressing RNF168 show altered DNA repair and responses to genotoxic treatments, genomic instability and resistance to proteotoxic stress. Oncogene 43 27841863
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
2019 PML nuclear bodies are recruited to persistent DNA damage lesions in an RNF168-53BP1 dependent manner and contribute to DNA repair. DNA repair 37 31009828
2011 Recruitment of the cohesin loading factor NIPBL to DNA double-strand breaks depends on MDC1, RNF168 and HP1γ in human cells. Biochemical and biophysical research communications 37 21784059
2019 A PRMT5-RNF168-SMURF2 Axis Controls H2AX Proteostasis. Cell reports 36 31533041
2016 RNF168 cooperates with RNF8 to mediate FOXM1 ubiquitination and degradation in breast cancer epirubicin treatment. Oncogenesis 32 27526106
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
2014 An RNF168 fragment defective for focal accumulation at DNA damage is proficient for inhibition of homologous recombination in BRCA1 deficient cells. Nucleic acids research 30 24829461
2013 RNF168 forms a functional complex with RAD6 during the DNA damage response. Journal of cell science 29 23525009
2014 Regulation of 53BP1 protein stability by RNF8 and RNF168 is important for efficient DNA double-strand break repair. PloS one 28 25337968
2020 Histone H2A variants alpha1-extension helix directs RNF168-mediated ubiquitination. Nature communications 27 32424115
2019 Cadmium disrupts the DNA damage response by destabilizing RNF168. Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association 27 31376412
2018 Structural insights into two distinct binding modules for Lys63-linked polyubiquitin chains in RNF168. Nature communications 26 29330428
2023 The HDAC6-RNF168 axis regulates H2A/H2A.X ubiquitination to enable double-strand break repair. Nucleic acids research 24 37503842
2022 A 1,2,3-Triazole Derivative of Quinazoline Exhibits Antitumor Activity by Tethering RNF168 to SQSTM1/P62. Journal of medicinal chemistry 24 36331508
2015 Ectopic expression of RNF168 and 53BP1 increases mutagenic but not physiological non-homologous end joining. Nucleic acids research 24 25916843
2021 New answers to the old RIDDLE: RNF168 and the DNA damage response pathway. The FEBS journal 22 33797206
2020 RNF168-Mediated Ubiquitin Signaling Inhibits the Viability of BRCA1-Null Cancers. Cancer research 21 32213544
2012 RNF8 and RNF168 but not HERC2 are required for DNA damage-induced ubiquitylation in chicken DT40 cells. DNA repair 21 23010445
2018 RNF168 facilitates proliferation and invasion of esophageal carcinoma, possibly via stabilizing STAT1. Journal of cellular and molecular medicine 20 30506884
2018 RNF126 Quenches RNF168 Function in the DNA Damage Response. Genomics, proteomics & bioinformatics 20 30529286
2017 Novel Combined Immune Deficiency and Radiation Sensitivity Blended Phenotype in an Adult with Biallelic Variations in ZAP70 and RNF168. Frontiers in immunology 20 28603521
2012 Structural basis for role of ring finger protein RNF168 RING domain. Cell cycle (Georgetown, Tex.) 20 23255131
2020 Ectopic RNF168 expression promotes break-induced replication-like DNA synthesis at stalled replication forks. Nucleic acids research 19 32182354
2024 Mechanisms of RNF168 nucleosome recognition and ubiquitylation. Molecular cell 18 38242129
2024 Mechanism of nucleosomal H2A K13/15 monoubiquitination and adjacent dual monoubiquitination by RNF168. Nature chemical biology 18 39394267
2024 Promotion of RNF168-Mediated Nucleosomal H2A Ubiquitylation by Structurally Defined K63-Polyubiquitylated Linker Histone H1. Angewandte Chemie (International ed. in English) 16 39363740
2015 Identification of RNF168 as a PML nuclear body regulator. Journal of cell science 16 26675234
2015 Ubiquitin-H2AX fusions render 53BP1 recruitment to DNA damage sites independent of RNF8 or RNF168. Cell cycle (Georgetown, Tex.) 15 25695757
2021 RNF168 is highly expressed in esophageal squamous cell carcinoma and contributes to the malignant behaviors in association with the Wnt/β-catenin signaling pathway. Aging 13 33493132
2024 Ubiquitin-induced RNF168 condensation promotes DNA double-strand break repair. Proceedings of the National Academy of Sciences of the United States of America 12 38968116
2018 RNF168 facilitates oestrogen receptor ɑ transcription and drives breast cancer proliferation. Journal of cellular and molecular medicine 12 29974997
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
2021 RNF168 E3 ligase participates in ubiquitin signaling and recruitment of SLX4 during DNA crosslink repair. Cell reports 11 34706224
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
2023 Emerging Roles of RNF168 in Tumor Progression. Molecules (Basel, Switzerland) 10 36771081
2018 A Novel Reciprocal Crosstalk between RNF168 and PARP1 to Regulate DNA Repair Processes. Molecules and cells 10 30037213
2017 Clinical and Biological Manifestation of RNF168 Deficiency in Two Polish Siblings. Frontiers in immunology 10 29255463
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
2016 An E2-guided E3 Screen Identifies the RNF17-UBE2U Pair as Regulator of the Radiosensitivity, Immunodeficiency, Dysmorphic Features, and Learning Difficulties (RIDDLE) Syndrome Protein RNF168. The Journal of biological chemistry 9 27903633
2024 A Site-Specific Click Chemistry Approach to Di-Ubiquitylate H1 Variants Reveals Position-Dependent Stimulation of the DNA Repair Protein RNF168. Angewandte Chemie (International ed. in English) 8 39377639
2023 Degradation of Ubiquitin-Editing Enzyme A20 following Autophagy Activation Promotes RNF168 Nuclear Translocation and NF-κB Activation in Lupus Nephritis. Journal of innate immunity 7 36944318
2021 RNF168 promotes RHOC degradation by ubiquitination to restrain gastric cancer progression via decreasing HDAC1 expression. Biochemical and biophysical research communications 7 33865221
2021 RNF168 suppresses the cancer stem cell-like traits of nonsmall cell lung cancer cells by mediating RhoC ubiquitination. Environmental toxicology 7 34873829
2024 A RAD18-UBC13-PALB2-RNF168 axis mediates replication fork recovery in BRCA1-deficient cancer cells. Nucleic acids research 6 38943334
2023 UBA80 and UBA52 fine-tune RNF168-dependent histone ubiquitination and DNA repair. The Journal of biological chemistry 6 37451480
2014 The ubiquitin ligases RNF8 and RNF168 display rapid but distinct dynamics at DNA repair foci in living cells. The international journal of biochemistry & cell biology 6 25304081
2024 PCNA-binding activity separates RNF168 functions in DNA replication and DNA double-stranded break signaling. Nucleic acids research 5 39445802
2025 PIN1-SUMO2/3 motif suppresses excessive RNF168 chromatin accumulation and ubiquitin signaling to promote IR resistance. Nature communications 4 40229270
2024 UBE2D3 facilitates NHEJ by orchestrating ATM signalling through multi-level control of RNF168. Nature communications 4 38866770
2021 MRE11 and UBR5 Co-Operate to Suppress RNF168-Mediated Fusion of Dysfunctional Telomeres. Frontiers in oncology 4 34881184
2019 Context Matters: RNF168 Connects with PALB2 to Rewire Homologous Recombination in BRCA1 Haploinsufficiency. Molecular cell 4 30901561
2019 SET8 localization to chromatin flanking DNA damage is dependent on RNF168 ubiquitin ligase. Cell cycle (Georgetown, Tex.) 4 31760894
2018 Calling RNF168 to action. Cell stress 4 31225475
2017 Retroviral insertional mutagenesis implicates E3 ubiquitin ligase RNF168 in the control of cell proliferation and survival. Bioscience reports 4 28754805
2025 TRIM39-mediated deubiquitination upregulates RNF168 to evade autophagy-ferroptosis in triple-negative breast cancer. NPJ breast cancer 1 41034232
2020 Not Black or White but Shades of Gray: Homologous Recombination Deficiency as a Continuous Variable Modulated by RNF168. Cancer research 1 32616507
2026 RNF168 promotes chronic colitis through ANXA7-mediated autophagy and NLRP3-driven pyroptosis. Apoptosis : an international journal on programmed cell death 0 41518435
2026 Targeting the USP7-PRMT6 epigenetic axis overcomes chemoresistance in breast cancer by coordinating H3R2me2a deposition and RNF168 methylation for DNA repair and ferroptosis blockade. Cell death and differentiation 0 41617976
2026 Lupenone regulates LOXL2-mediated PANoptosis signaling through E3 ubiquitin ligases RNF168 to improve radiation-induced lung injury. Phytomedicine : international journal of phytotherapy and phytopharmacology 0 41722124
2026 Ubiquitin-dependent recruitment of SLFN11 to chromatin is regulated by deubiquitinase (DUB) and RNF168. bioRxiv : the preprint server for biology 0 41929013
2025 RNF168 dephosphorylation ameliorates cognitive decline in Aβ-based mouse models of Alzheimer's disease. Acta neuropathologica communications 0 40993809
2023 Topology of Ubiquitin Chains in the Chromatosomal Environment of the E3 Ubiquitin Ligase RNF168. Biochemistry. Biokhimiia 0 38462450