Affinage

DDB2

DNA damage-binding protein 2 · UniProt Q92466

Length
427 aa
Mass
47.9 kDa
Annotated
2026-06-09
100 papers in source corpus 50 papers cited in narrative 50 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 9/10 claims corpus-supported (90%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

DDB2 (XPE/p48) is the DNA-damage-recognition subunit of the CRL4(DDB2) E3 ubiquitin ligase that initiates global-genome nucleotide excision repair (GG-NER) of UV photolesions (PMID:19109893, PMID:20368362). Its WD40 domain binds the lesion directly, inserting a hairpin into the minor groove to extrude the photodimer into a binding pocket and kink the duplex, enabling detection of helix-distorting lesions including CPDs, 6-4PPs, abasic sites, and mismatches that other surveillance proteins miss (PMID:19109893, PMID:16223728). Both DDB1 and DDB2 subunits are required for damaged-DNA binding, and XP-E patient mutations abolish this activity (PMID:10777490). Within the complex DDB2 partners with DDB1, CUL4A, and Roc1 to form an active E3 ligase whose output is gated by the COP9 signalosome (PMID:12732143). DDB2 opens chromatin at damage sites by promoting PARP1-dependent poly(ADP-ribosyl)ation and recruitment of the remodeler ALC1, a chromatin-decondensation function separable from its ligase activity (PMID:23045548, PMID:22492724), and it then hands the lesion to XPC—DDB2 being required to recruit XPC and downstream factors (XPA) to CPD sites (PMID:12944386, PMID:20368362, PMID:14742321). Productive handover requires timely DDB2 turnover: CUL4A-mediated ubiquitylation of the DDB2 N-terminal tail drives its dissociation and proteasomal degradation, with p97/VCP segregating it from chromatin and TFIIH arrival stabilizing the XPC-TFIIH verification complex (PMID:11564859, PMID:32985517, PMID:25628365, PMID:24770583). This turnover is tuned by a dense regulatory layer—XPC/centrin-2 competitive protection (PMID:25628365), SIRT6 deacetylation (PMID:32789493), PARsylation, α-N-methylation, SUMOylation by PIASy (PMID:23045548, PMID:24753253, PMID:28981631, PMID:23860269), and deubiquitination by USP24 and USP44 (PMID:23159851, PMID:33937266). Beyond repair, DDB2 expression is induced by p53 (PMID:11971958), and DDB2 in turn directs CRL4 to degrade p21 and modulate p53, governing the apoptosis-versus-arrest cell-fate decision after DNA damage (PMID:17967871, PMID:19541625). DDB2 also acts as a chromatin-associated transcriptional regulator, repressing antioxidant genes, EMT drivers, HIF1A, and ALDH1A1 through recruitment of Suv39h/EZH2 and repressive histone methylation, while activating IκBα and RNF43 (PMID:20351176, PMID:23610444, PMID:29752431, PMID:31740787, PMID:29021137, PMID:23774208). Inactivating DDB2 mutations underlie the xeroderma pigmentosum complementation group E (XP-E) defect in UV-damaged DNA binding and repair (PMID:10777490).

Mechanistic history

Synthesis pass · year-by-year structured walk · 18 steps
  1. 2000 High

    Established that DDB2 is the subunit responsible for UV-damaged DNA binding and that its loss explains the XP-E repair defect, defining DDB2's core biochemical identity.

    Evidence Baculovirus reconstitution of individual subunits, EMSA with UV-damaged DNA, and complementation of XP-E extracts with patient-derived mutants

    PMID:10777490

    Open questions at the time
    • Did not resolve how the lesion is physically engaged
    • Did not define the larger E3 ligase context
  2. 2001 High

    Identified CUL4A as the E3 that targets DDB2 for proteasomal degradation and showed DDB2 controls DDB1 nuclear accumulation, linking DDB2 turnover and localization to the cullin machinery.

    Evidence Coexpression, ubiquitination assays, proteasome inhibition, binding-defective XP-E mutant, and deletion-mutant nuclear localization assays

    PMID:11564859 PMID:11581406

    Open questions at the time
    • Functional purpose of DDB2 degradation during repair not yet defined
    • DDB1-independent nuclear import role characterized only via HBx
  3. 2002 High

    Showed DDB2 is a transcriptional target of p53 (with BRCA1 enhancement), placing DDB2 induction within the DNA-damage response and explaining species differences in UV-inducible expression.

    Evidence p53 promoter-binding and reporter assays, ChIP, antisense BRCA1 knockdown, and human/mouse orthologous sequence comparison

    PMID:11971958 PMID:12170778

    Open questions at the time
    • BRCA1 contribution from single lab
    • Did not address reciprocal DDB2 regulation of p53
  4. 2003 High

    Defined DDB2 as the substrate-recognition subunit of a CUL4A-Roc1-DDB1 E3 ligase regulated by the COP9 signalosome, and showed DDB2 activates XPC recruitment to CPD lesions in cells.

    Evidence Reciprocal Co-IP, ubiquitin ligase activity assays, CSN RNAi with NER readout, and immunofluorescence in photolyase-expressing XP cells; plus DDB2-p53 mutual regulation in XP-E cells

    PMID:12732143 PMID:12944386 PMID:14560002

    Open questions at the time
    • Relevant in vivo ubiquitylation substrates at lesions not yet identified
    • p53 reciprocal regulation supported by single lab
  5. 2004 High

    Placed DDB2 downstream of p53 in driving the UV-induced chromatin redistribution of XPC, and identified dominant-negative splice variants, clarifying the DDB2-to-XPC handoff hierarchy.

    Evidence Chromatin fractionation, ectopic DDB2 rescue in p53-null cells, and RT-PCR/EMSA characterization of splice variants

    PMID:14742321 PMID:14751237

    Open questions at the time
    • Molecular basis of XPC redistribution not yet defined
    • Physiological abundance of dominant-negative variants unknown
  6. 2005 High

    Reconstituted DDB2's lesion recognition as a structural-distortion sensor and confirmed the purified CUL4A E3 directly ubiquitylates DDB2, separating sensing from enzymatic output.

    Evidence In vitro reconstitution with purified subunits, EMSA across defined substrates, and in vitro ubiquitylation with purified E3

    PMID:15811626 PMID:16223728

    Open questions at the time
    • Specificity for genuine photolesions vs. mismatches in chromatin not resolved
    • Functional consequence of auto-ubiquitylation not addressed here
  7. 2006 High

    Demonstrated that CUL4A/DDB1-mediated DDB2 degradation at damage sites is required for XPC recruitment and CPD removal, and that DDB1 is needed for CUL4A translocation but not for DDB2's intrinsic DNA binding.

    Evidence siRNA and MG132 inhibition, chromatin fractionation, micropore-irradiation immunofluorescence, CPD repair assays, plus Claspin Co-IP/knockdown

    PMID:16527807 PMID:16951172 PMID:17196446

    Open questions at the time
    • Why degradation aids handover rather than ending recognition not yet mechanistically resolved
    • Claspin role from single lab
  8. 2007 High

    Quantified DDB2 lesion-binding kinetics and showed DDB2 licenses NER by degrading p53/limiting p21, preventing p21-mediated PCNA sequestration, linking DDB2 turnover to repair competence.

    Evidence FRAP and live-cell imaging of tagged DDB2; DDB2-/- and p21-/- MEF epistasis with NER assays

    PMID:17635991 PMID:17967871

    Open questions at the time
    • Trigger coupling lesion residence to degradation not identified
    • p53/p21 axis tested in mouse cells
  9. 2008 High

    Provided the atomic mechanism of lesion recognition (hairpin insertion/extrusion, duplex kinking) and identified p38 MAPK as an upstream signal driving DDB2 ubiquitylation, chromatin relaxation, and repair.

    Evidence X-ray crystallography of DDB1-DDB2-DNA complexes with functional validation; p38 inhibitor with phosphorylation, ubiquitination, and CPD repair readouts; FRAP of DDB1 controlled by DDB2 levels

    PMID:18806262 PMID:18936169 PMID:19109893

    Open questions at the time
    • p38 phosphosite on DDB2 not mapped (Medium-confidence study)
    • Structural model from purified components without chromatin context
  10. 2010 High

    Showed the ligase activity is required for chromatin GG-NER and recruits XPA, with XPC/Ku oppositely tuning activity; and revealed a transcriptional repressor role at antioxidant genes via Suv39h/H3K9me3.

    Evidence In vivo ubiquitination with XP-E mutant complementation, chromatin fractionation, XPA recruitment; and ChIP/ROS/senescence assays in DDB2-deficient cells

    PMID:20351176 PMID:20368362

    Open questions at the time
    • Histone substrates of the ligase at lesions not fully defined
    • Antioxidant-gene repression from single lab (Medium)
  11. 2012 High

    Separated DDB2's PARP1/ALC1-driven large-scale chromatin decondensation from its ligase activity, and identified PARsylation, USP24 deubiquitination, and a p21-degradation cell-fate function as regulators of DDB2 stability and outcome.

    Evidence Chromatin-unfolding assays in DDB2-deficient cells with PARP inhibition; Co-IP/PAR assays/ALC1 depletion; USP24 yeast two-hybrid and in vitro deubiquitination; DDB2-deficient apoptosis/arrest analysis

    PMID:19541625 PMID:22492724 PMID:23045548 PMID:23159851

    Open questions at the time
    • How decondensation and ligase functions are coordinated unclear
    • USP24 and p21 cell-fate findings from single labs (Medium)
  12. 2013 Medium

    Expanded DDB2's regulatory repertoire to PIASy-mediated SUMOylation for CPD repair, PCNA-PIP-box-coupled degradation, checkpoint kinase (ATR/ATM) activation, and transcriptional control of EMT, NF-κB/IκBα, and NEDD4L/TGF-β.

    Evidence PIASy RNAi with lesion-specific repair; PIP-box mutagenesis and PCNA RNAi; ATR/ATM Co-IP and DDB2/XPC knockdown; EMT and IκBα/NF-κB and NEDD4L/EZH2 ChIP and functional assays

    PMID:23422745 PMID:23610444 PMID:23774208 PMID:23860269 PMID:24200966 PMID:26130719

    Open questions at the time
    • Each regulatory and transcriptional arm rests on a single lab
    • Direct vs. indirect transcriptional targeting not always resolved
  13. 2014 High

    Identified non-degradative DDB2 modifications and cofactors—α-N-trimethylation, p97/VCP segregase extraction—that govern its localization, recruitment, ATM activation, and timely chromatin removal.

    Evidence Mass spectrometry and in vitro methylation with methylation-defective mutant; p97 knockdown with DDB2/XPC epistasis, chromatin fractionation, and chromosomal aberration analysis

    PMID:24753253 PMID:24770583

    Open questions at the time
    • Interplay between methylation and ubiquitination not resolved
    • Functional importance of α-N-methylation tested in one system
  14. 2015 Medium

    Defined the DDB2 N-terminal lysine tail as the major ubiquitination site under XPC/centrin-2 competitive protection, and extended CRL4(DDB2) substrate range to AR, PAQR3, and TGF-β regulators.

    Evidence DDB2 N-terminal mutants, in vitro competitive ubiquitination with XPC/centrin-2; Co-IP and ubiquitination assays for AR (prostate cells) and PAQR3 (epistasis), plus NEDD4L transcriptional work

    PMID:22846800 PMID:25628365 PMID:26205499

    Open questions at the time
    • Substrate-targeting findings (AR, PAQR3) each from a single lab
    • Physiological selectivity among the many proposed substrates unclear
  15. 2017 Medium

    Established SUMOylation at K309 as essential for XPC recruitment and CPD repair, and identified a CUL4-independent DDB2-Ku (XRCC5/6) axis driving SEMA3A transcription.

    Evidence In vitro/in vivo SUMOylation with K309R mutant and repair readout; Co-IP, chromatin fractionation, and ChIP at the SEMA3A promoter

    PMID:28035050 PMID:28981631

    Open questions at the time
    • Both findings from single labs
    • Relationship between SUMOylation and ubiquitination/degradation timing unresolved
  16. 2019 Medium

    Broadened DDB2's transcriptional and substrate roles to HIF1A repression via Suv39h1/H3K9me3 and CRL4-mediated LRH-1 degradation affecting glucose metabolism.

    Evidence ChIP for DDB2/H3K9me3 at HIF1A with xenograft readout; Co-IP, ubiquitination, and glucose-metabolism assays for LRH-1

    PMID:30923324 PMID:31740787

    Open questions at the time
    • Each role from a single lab
    • Direct vs. indirect mechanism for metabolic effects not fully dissected
  17. 2020 High

    Resolved the kinetic logic of repair handover—ubiquitylation-driven DDB2 dissociation enabling XPC-TFIIH verification—and added SIRT6 deacetylation and EZH2 stabilization as upstream controls of DDB2 retention.

    Evidence Live-cell imaging, FRAP, and ubiquitination manipulation; SIRT6 Co-IP/deacetylation with K35/K77 mutants; EZH2 Co-IP, ubiquitination, and cisplatin-sensitivity epistasis

    PMID:32457468 PMID:32789493 PMID:32985517

    Open questions at the time
    • SIRT6 and EZH2 contributions from single labs (Medium)
    • Quantitative ordering of all modifications at a single lesion not established
  18. 2021 Medium

    Identified additional turnover regulators (USP44 deubiquitination, MEKK1-driven CRL4 autoubiquitination) and a new substrate (CDT2 linking DDB2 to replication licensing), extending its DNA-damage and cell-cycle roles.

    Evidence In vitro deubiquitination and USP44 KO cells/mice with tumor incidence; MEKK1 Co-IP and ubiquitin-linkage replacement; CDT2 Co-IP, ubiquitination, PIP-box mutant, and cell-cycle analysis

    PMID:33557942 PMID:33937266 PMID:34251884

    Open questions at the time
    • MEKK1 and CDT2 findings from single labs
    • Integration of K63-linked chains into DDB2 fate not fully resolved

Open questions

Synthesis pass · forward-looking unresolved questions
  • How DDB2's dual repair-ligase and transcriptional-regulator activities are coordinated, and which of its many proposed CRL4 substrates and transcriptional targets are physiologically dominant in a given tissue, remains unresolved.
  • No unified model relating chromatin opening, ubiquitylation, and transcriptional repression
  • Many substrate/target relationships rest on single-lab evidence
  • Tissue-specific selectivity of substrate engagement unknown

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140110 transcription regulator activity 5 GO:0140096 catalytic activity, acting on a protein 4 GO:0003677 DNA binding 3 GO:0042393 histone binding 3 GO:0016874 ligase activity 2 GO:0140097 catalytic activity, acting on DNA 2
Localization
GO:0000228 nuclear chromosome 4 GO:0005634 nucleus 3 GO:0005654 nucleoplasm 2
Pathway
R-HSA-74160 Gene expression (Transcription) 6 R-HSA-4839726 Chromatin organization 5 R-HSA-392499 Metabolism of proteins 4 R-HSA-73894 DNA Repair 4 R-HSA-8953897 Cellular responses to stimuli 3 R-HSA-5357801 Programmed Cell Death 1
Partners
CUL4ADDB1EZH2PARP1PCNASIRT6USP44XPC
Complex memberships
CRL4(DDB2) (DDB1-DDB2-CUL4A-Roc1) E3 ubiquitin ligaseDDB1-DDB2 (UV-DDB) complex

Evidence

Reading pass · 50 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2008 Crystal structures of the DDB1-DDB2 complex alone and bound to DNA containing a 6-4PP lesion or abasic site revealed that the WD40 domain of DDB2 holds the lesion exclusively; a DDB2 hairpin inserts into the minor groove, extrudes the photodimer into a binding pocket, and kinks the duplex by ~40°, enabling DDB2 to detect lesions refractory to other surveillance proteins. X-ray crystallography with functional validation Cell High 19109893
2003 DDB2 and CSA are each integrated into nearly identical complexes via interaction with DDB1; both complexes contain cullin 4A and Roc1 and display E3 ubiquitin ligase activity; the COP9 signalosome (CSN) differentially regulates the ubiquitin ligase activity of the DDB2 and CSA complexes in response to UV irradiation; CSN knockdown by RNAi causes defects in NER. Co-immunoprecipitation, ubiquitin ligase activity assay, RNAi knockdown with NER functional readout Cell High 12732143
2003 In vivo, DDB2 (p48) localizes to UV-irradiated sites containing either CPDs or 6-4PPs; XPC localizes only to 6-4PP sites unless DDB2 is overexpressed, which then recruits XPC to CPD sites, demonstrating that DDB2 activates XPC recruitment to CPDs. Live-cell/fixed-cell immunofluorescence in repair-deficient XP-A cells expressing photolyases, overexpression of p48 The Journal of biological chemistry High 12944386
2005 Reconstituted DDB1-DDB2 complex binds UV-induced CPDs with ~6-fold higher affinity than undamaged DNA, binds 6-4PPs and abasic sites with high specificity, and also binds 2–3 bp mismatches; DDB1-DDB2 functions as a structural distortion sensor rather than a lesion-specific detector. In vitro reconstitution of DDB1-DDB2 with purified subunits; electrophoretic mobility shift assay with defined substrates The Journal of biological chemistry High 16223728
2001 Cullin 4A (CUL4A) is a specific E3 ubiquitin ligase targeting DDB2 for ubiquitination and proteasomal degradation; coexpression of CUL4A (but not Cul-1 or other related cullins) increases ubiquitination and decay rate of DDB2; a naturally occurring XP-E mutant of DDB2 (2RO) that does not bind CUL4A is unaffected. Coexpression, ubiquitination assay, proteasome inhibitor treatment, DDB2 mutant analysis Molecular and cellular biology High 11564859
2005 Purified CUL4A-containing E3 complex directly ubiquitylates DDB2 in vitro; reconstitution confirmed that the DDB-CUL4A E3 complex is sufficient for DDB2 ubiquitylation. In vitro ubiquitylation assay with purified E3 complex DNA repair High 15811626
2006 CUL4A mediates proteasomal degradation of DDB2 at UV-damage sites; blocking CUL4A (by siRNA or MG132) prolongs DDB2 retention at damage foci; CUL4A knockdown decreases XPC recruitment to damage sites and reduces CPD removal from the genome. siRNA knockdown, proteasome inhibitor, immunofluorescence at micropore-irradiated sites, CPD repair assay The Journal of biological chemistry High 16527807
2002 p53 directly binds and transcriptionally activates the human DDB2 gene via a p53-responsive element in the DDB2 promoter; the orthologous region in the mouse DDB2 gene does not support p53 binding or activation, explaining deficient UV-inducible DDB2 expression in mouse cells. p53 binding assay to DDB2 promoter sequences, transcriptional reporter assays, p53 protein accumulation vs. DDB2 mRNA in mouse cells Molecular and cellular biology High 11971958
2012 DDB2 facilitates poly(ADP-ribosyl)ation of UV-damaged chromatin via PARP1, leading to recruitment of the chromatin-remodeling enzyme ALC1; DDB2 itself is targeted by poly(ADP-ribosyl)ation, increasing its protein stability and prolonged chromatin retention by suppressing DDB2 ubiquitylation. Co-immunoprecipitation, in vitro and in vivo PAR assay, ALC1 depletion with UV sensitivity readout The Journal of cell biology High 23045548
2012 DDB2 promotes large-scale chromatin decondensation at UV-induced lesions independently of the CRL4 ubiquitin ligase complex; this requires PARP1 activity; XPC lesion recognition (but not DDB2) requires ATP-dependent processes and is regulated by steady-state PAR levels. Fluorescence-based chromatin unfolding assay, DDB2-deficient cells, PARP1 inhibition, ATP depletion The Journal of cell biology High 22492724
2007 In vivo, the majority of DDB2 diffuses in the nucleus as part of a high-molecular-mass complex; essentially all DDB2 binds UV-induced damage with ~2-minute residence time; DDB2 is proteolytically degraded with a half-life much longer than its residence time on a lesion, indicating that damaged-DNA binding is not the primary trigger for DDB2 degradation; DDB2 binding to/dissociation from lesions is independent of XPC. Fluorescence recovery after photobleaching (FRAP), live-cell imaging of fluorescently tagged DDB2, local UV irradiation Journal of cell science High 17635991
2014 p97/VCP/Cdc48 segregase complex is required for timely removal of DDB2 and XPC from chromatin; prolonged retention due to p97 deficiency impairs DNA excision repair; chromosomal aberrations caused by excess chromatin-retained DDB2 are alleviated by concurrent DDB2 downregulation. p97 knockdown, DDB2/XPC knockdown epistasis, chromatin fractionation, NER assay, chromosomal aberration analysis Nature communications High 24770583
2020 Timely DDB2 dissociation from UV lesions is required for DNA damage handover to XPC; DDB2 ubiquitylation promotes its dissociation/degradation to prevent excessive lesion re-binding; arrival of TFIIH further promotes DDB2 dissociation and formation of a stable XPC-TFIIH damage-verification complex. Live-cell imaging, ubiquitination assays, FRAP, genetic manipulation of DDB2 degradation Nature communications High 32985517
2020 SIRT6 interacts with DDB2 (interaction enhanced upon UV), deacetylates DDB2 at K35 and K77 upon UV stress, thereby promoting DDB2 ubiquitination and segregation from chromatin to facilitate downstream NER signaling. Co-immunoprecipitation, in vitro deacetylation assay, mutagenesis of K35 and K77, chromatin fractionation, NER assay Nucleic acids research High 32789493
2014 The N-terminal alanine of DDB2 (after Met removal) is trimethylated on its α-amino group by the N-terminal RCC1 methyltransferase; a methylation-defective DDB2 mutant shows diminished nuclear localization, reduced recruitment to CPD foci, compromised ATM activation, decreased CPD repair efficiency, and elevated UV sensitivity. Mass spectrometry, in vitro methylation assay, methylation-defective mutant expression, immunofluorescence at CPD foci, ATM activation and repair assay The Journal of biological chemistry High 24753253
2015 The N-terminal tail of DDB2 (containing seven lysines) is the major site for CUL4-mediated ubiquitination targeting DDB2 for proteasomal degradation; XPC competitively suppresses DDB2 ubiquitination in vitro, an effect augmented by centrin-2; XPC thereby protects DDB2 from degradation, allowing multiple rounds of repair. Exogenous expression of mutant DDB2 in fibroblasts, in vitro ubiquitination competition assay, XPC/centrin-2 addition Nucleic acids research High 25628365
2017 DDB2 is SUMOylated at Lys-309 upon UV irradiation; SUMOylation depends on DDB2 binding to damaged chromatin and an active 26S proteasome; SUMO-1 conjugation is the major modification; K309R mutant DDB2 loses ability to recruit XPC to damage sites and to repair CPDs. In vitro and in vivo SUMOylation assay, K309R mutagenesis, XPC localization assay, CPD repair assay Carcinogenesis High 28981631
2013 DDB2 SUMOylation (by PIASy as major SUMO E3 ligase) is UV-dependent; PIASy knockdown reduces CPD removal from the genome but does not affect 6-4PP removal, indicating that PIASy-mediated DDB2 SUMOylation is specifically required for CPD repair. RNAi knockdown of PIASy, CPD and 6-4PP repair assays, Co-immunoprecipitation of DDB2-PIASy Biochemical and biophysical research communications Medium 23860269
2010 The ubiquitin ligase activity of the DDB2 complex is required for efficient GG-NER in chromatin; XP-E patient-derived mutant DDB2 proteins fail to mediate ubiquitylation at damage sites; CSN dissociates from the DDB2 complex upon binding to damaged DNA; XPC and Ku oppositely regulate DDB2 complex ubiquitin ligase activity at damaged sites; DDB2 complex-mediated ubiquitylation recruits XPA to damaged sites. In vivo ubiquitination assay, mutant DDB2 complementation, chromatin fractionation, XPA recruitment assay Molecular and cellular biology High 20368362
2008 p38 MAPK phosphorylates DDB2 and mediates UV-induced DDB2 ubiquitylation and degradation; p38 MAPK inhibition (SB203580) impairs DDB2 degradation, histone H3 acetylation/chromatin relaxation, XPC and TFIIH recruitment to UV-damage sites, and CPD repair. p38 MAPK inhibitor, phosphorylation assay, ubiquitination assay, chromatin relaxation assay, immunofluorescence recruitment assay, CPD repair The Journal of biological chemistry Medium 18806262
2013 DDB2 association with PCNA via a PIP-box in its N-terminal region is required for DDB2 proteasomal degradation after UV; mutation of the PIP-box or PCNA depletion by RNAi greatly impairs UV-induced DDB2 degradation; DDB2 co-localizes with PCNA and p21 at local UV-damage sites; p21 requires PCNA (not direct DDB2 binding) to form a trimeric complex with DDB2. PIP-box mutagenesis, PCNA RNAi, co-immunoprecipitation, in vitro binding assay with recombinant proteins, immunofluorescence Cell cycle High 24200966
2006 DDB1 is required for UV-induced DDB2 ubiquitylation and degradation; DDB1 knockdown impairs CUL4A translocation to UV-damaged chromatin but does not affect DDB2's intrinsic DNA damage-binding activity (DDB2 can bind damaged DNA as a monomer in vivo); DDB1 is critical for NER of CPDs but not 6-4PPs. DDB1 siRNA knockdown, chromatin fractionation, UV lesion repair assay, local UV irradiation foci analysis Cancer research High 16951172
2004 UV radiation causes XPC translocation from loosely-bound to tightly chromatin-associated form; this redistribution requires both p53 and DDB2; ectopic DDB2 expression in p53-deficient cells rescues XPC translocation and recruitment to damage sites, placing DDB2 downstream of p53 in regulating XPC. Chromatin fractionation, immunofluorescence at local UV damage sites, ectopic DDB2 expression in p53-null cells Carcinogenesis High 14742321
2007 DDB2 participates in NER by regulating cellular levels of p21(Waf1/Cip1): DDB2 enhances DDB1 nuclear accumulation, which targets phospho-Ser18-p53 for degradation, suppressing p21 expression; elevated p21 in DDB2-deficient MEFs causes NER deficiency, reversed by p21 deletion or knockdown; DDB2 thereby licenses NER by preventing PCNA sequestration by p21. DDB2-/- and p21-/- mouse embryonic fibroblasts (genetic epistasis), DDB1 fractionation, p21 knockdown rescue of NER, in vitro/in vivo NER assay Molecular and cellular biology High 17967871
2009 DDB2 targets p21(Waf1/Cip1) for proteasomal degradation via the CUL4A-DDB1 E3 ligase; this regulatory function of DDB2 defines the cell fate decision between apoptosis and cell cycle arrest after DNA damage; DDB2-deficient cells show increased p21, resist apoptosis (including E2F1-induced apoptosis), and undergo cell cycle arrest instead; Mdm2 is involved in DDB2-dependent apoptosis in a p53-independent manner. DDB2-deficient cell analysis, p21 proteolysis assay, DDB2 overexpression and knockdown, E2F1 apoptosis assay Proceedings of the National Academy of Sciences of the United States of America High 19541625
2003 DDB2 directly regulates p53 levels before and after UV irradiation (via an intron 4 p53-binding element); XP-E cells are defective in UV-induced apoptosis due to severely reduced basal and UV-induced p53 levels; these defects are restored by DDB2 cDNA constructs containing intron 4, establishing mutual regulatory interactions between DDB2 and p53. DDB2 expression constructs (with/without intron 4), p53 protein level measurement, apoptosis assay in XP-E cells Molecular and cellular biology Medium 14560002
2002 BRCA1 enhances p53 binding to the DDB2 promoter and p53-dependent transactivation of DDB2 promoter-reporter constructs; antisense BRCA1 abrogates UV-induced DDB2 upregulation; reduced BRCA1-dependent DDB2 function delays CPD and 6-4PP removal. Chromatin immunoprecipitation (p53 at DDB2 promoter), promoter-reporter assay, antisense BRCA1 knockdown, photoproduct repair assay Cancer biology & therapy Medium 12170778
2012 Deubiquitinating enzyme USP24 interacts with DDB2; USP24 knockdown decreases steady-state DDB2 levels; USP24 cleaves ubiquitinated DDB2 in vitro, indicating USP24 stabilizes DDB2 by preventing its ubiquitin-mediated degradation. Yeast two-hybrid, co-immunoprecipitation, USP24 knockdown, in vitro deubiquitination assay Cell cycle Medium 23159851
2021 Deubiquitinase USP44 directly deubiquitinates DDB2 to prevent its premature degradation; USP44-deficient cells show impaired DDB2 accumulation at DNA lesions, reduced XPC retention, and defective CPD repair; Usp44-knockout mice are prone to UV- and DMBA-induced tumors. In vitro deubiquitination assay, USP44 knockout cells/mice, DDB2 accumulation at foci, CPD repair assay, tumor incidence Frontiers in cell and developmental biology High 33937266
2013 DDB2 and XPC are required for damage-specific ATR and ATM recruitment and phosphorylation at UV-damage sites; ATR and ATM physically interact with XPC; in DDB2-deficient cells, ATR/ATM recruitment and phosphorylation of their substrates (Chk1, Chk2, H2AX, BRCA1) are reduced; ATR/ATM deficiency does not affect DDB2 or XPC recruitment, placing DDB2/XPC upstream of checkpoint kinase activation. Co-immunoprecipitation of ATR/ATM with XPC, local UV irradiation immunofluorescence, DDB2/XPC knockdown, ATR/ATM-deficient cells DNA repair Medium 23422745
2010 DDB2 represses antioxidant genes by recruiting CUL4A and Suv39h and increasing histone H3K9 trimethylation at their promoters; DDB2-deficient cells fail to accumulate ROS and do not undergo premature senescence; DDB2 expression is itself induced by ROS, forming a positive feedback loop. DDB2-deficient cells, ChIP for H3K9me3 at antioxidant gene promoters, ROS measurement, senescence assay Molecular and cellular biology Medium 20351176
2013 DDB2 constitutively represses EMT-regulatory genes in colon cancer cells; DDB2 depletion promotes mesenchymal phenotype while DDB2 re-expression restores epithelial phenotype; DDB2 inhibits EMT induced by hypoxia and TGF-β. DDB2 knockdown/overexpression with EMT marker analysis (qPCR, immunofluorescence), invasion assay, xenograft metastasis model Cancer research Medium 23610444
2013 DDB2 decreases NF-κB activity by upregulating IκBα transcription through direct binding to the IκBα proximal promoter; this suppresses MMP9 expression and limits breast tumor cell invasiveness; knockdown of DDB2-induced IκBα restores NF-κB activity and invasive properties. DDB2 overexpression/knockdown, promoter binding assay (ChIP), invasion assay, NF-κB activity reporter, IκBα rescue experiment Cancer research Medium 23774208
2015 DDB2 binds the NEDD4L promoter and recruits EZH2 to repress NEDD4L transcription by enhancing H3K27me3 at the NEDD4L promoter; repression of NEDD4L by DDB2 enhances TGF-β signal transduction in ovarian cancer cells. ChIP for DDB2 and H3K27me3 at NEDD4L promoter, EZH2 co-immunoprecipitation, TGF-β signaling assays, DDB2 knockdown/overexpression Nucleic acids research Medium 26130719
2017 DDB2 recruits EZH2 and β-catenin to an upstream site in the Rnf43 gene, enabling interaction with distant TCF4/β-catenin binding sites in the Rnf43 intron to activate RNF43 expression, which restricts Wnt signaling; DDB2-deficient mice show increased susceptibility to colon tumor development with elevated Wnt pathway activation. ChIP for DDB2/EZH2/β-catenin at Rnf43 locus, DDB2-knockout mice, Wnt reporter assays, tumor incidence Cancer research Medium 29021137
2020 EZH2 forms a complex with DDB1-DDB2 and stabilizes DDB2 by impairing its ubiquitination independently of its methyltransferase activity and PRC2 complex; EZH2 depletion reduces DDB2 localization to CPD crosslinks and impairs their repair; this activity is epistatic with DDB1-DDB2 for cisplatin sensitivity. Co-immunoprecipitation, ubiquitination assay, EZH2 depletion with DDB2 stability readout, synthetic lethality screen, CPD immunofluorescence, epistasis Oncogene Medium 32457468
2015 DDB2 interacts with the androgen receptor (AR), mediates contact between AR and the CUL4A-DDB1 complex, and promotes AR ubiquitination and proteasomal degradation; DNA damage-induced DDB2 expression reduces AR protein levels via this mechanism; DDB2 inhibits growth of AR-expressing prostate cancer cells (LNCaP) but not AR-null cells (PC3). Co-immunoprecipitation, ubiquitination assay, DDB2 overexpression in prostate cancer cell lines, cell growth assay The international journal of biochemistry & cell biology Medium 22846800
2019 DDB2 directly interacts with LRH-1 (liver receptor homologue-1) and functions as the substrate recognition component of CUL4-DDB1 to promote LRH-1 ubiquitination and proteasomal degradation; DDB2 overexpression reduces insulin-stimulated LRH-1 levels and decreases glucokinase expression; DDB2 knockdown increases glucose uptake and intracellular glucose-6-phosphate. Co-immunoprecipitation, ubiquitination assay, DDB2 overexpression/knockdown, gene expression and glucose metabolism assays Scientific reports Medium 30923324
2015 DDB2 is involved in ubiquitination and degradation of PAQR3; DDB2 interacts with PAQR3 in vivo and in vitro; DDB2 controls PAQR3 protein stability and polyubiquitination; Lys-61 of PAQR3 is the target site; DDB2 knockdown decreases cancer cell proliferation and migration in a PAQR3-dependent manner. Co-immunoprecipitation, in vitro interaction assay, ubiquitination assay, Lys-61 mutation, DDB2/PAQR3 double knockdown epistasis The Biochemical journal Medium 26205499
2021 CRL4-DDB2 is a novel E3 ubiquitin ligase for CDT2; DDB2 overexpression enhances CDT2 ubiquitination and degradation via a PIP-box-independent mechanism; DDB2 knockdown stabilizes CDT2 and arrests the cell cycle in G1; this pathway indirectly regulates CDT1 stability and pre-replication complex assembly. Co-immunoprecipitation, in vivo ubiquitination assay, DDB2 knockdown/overexpression, PIP-box mutant, cell cycle analysis Cell & bioscience Medium 33557942
2016 UVRAG localizes to photolesions, associates with DDB1, and promotes assembly and activity of the DDB2-DDB1-CUL4A-ROC1 (CRL4-DDB2) ubiquitin ligase complex, leading to efficient XPC recruitment and global genome NER; UVRAG depletion decreases substrate handover to XPC. Co-immunoprecipitation of UVRAG with DDB1, local UV irradiation immunofluorescence, UVRAG depletion with NER and XPC recruitment readout, Drosophila genetic model Molecular cell Medium 27203177
2006 Claspin physically associates with DDB1 and DDB2 and is required for UV-induced DDB2 degradation and co-localization of DDB2 to damage sites; Claspin knockdown abolishes UV-induced DDB2 turnover at damage foci but does not affect XPC levels or XPC co-localization with lesions. Claspin siRNA knockdown, DDB2 degradation assay, immunofluorescence co-localization, co-immunoprecipitation DNA repair Medium 17196446
2016 DDB2 associates with XRCC5/6 (Ku70/Ku80) in a CUL4-independent and DNA-PKcs-independent manner; in the absence of DNA damage, chromatin association of XRCC5 requires DDB2; DDB2 recruits XRCC5 to the SEMA3A gene promoter to activate its transcription; XRCC5 depletion inhibits SEMA3A expression without affecting VEGFA (a DDB2-repressed gene). Co-immunoprecipitation, chromatin fractionation, DDB2 knockdown with XRCC5 localization readout, ChIP at SEMA3A promoter Molecular biology of the cell Medium 28035050
2021 MEKK1 kinase constitutively interacts with a cytosolic CRL4 complex and is cleaved by caspases after DNA damage; MEKK1 kinase activity triggers autoubiquitination of the CRL4 complex; MEKK1 knockdown prevents DNA damage-induced degradation of DDB2 and p21; K63-linked ubiquitin chains contribute to DDB2/p21 decay and cell survival. Co-immunoprecipitation, ubiquitin-linkage replacement strategy, MEKK1 knockdown, DDB2 degradation assay, cell survival assay Molecular and cellular biology Medium 34251884
2018 DDB2 binds to the ALDH1A1 gene promoter, facilitates H3K27me3 enrichment at this region, and competes with the transcription factor C/EBPβ for binding, thereby repressing ALDH1A1 transcription and suppressing cancer stem cell dedifferentiation in ovarian cancer cells. ChIP for DDB2 and H3K27me3 at ALDH1A1 promoter, DDB2/C/EBPβ competition assay, DDB2 overexpression/knockdown with ALDH1A1 expression and CSC phenotype readout Cell death & disease Medium 29752431
2019 DDB2 binds to an upstream promoter element in the HIF1A gene and recruits Suv39h1 to promote H3K9me3, repressing HIF1α mRNA expression in both normoxia and hypoxia; DDB2 knockdown enhances angiogenic marker expression and promotes xenograft tumor growth. ChIP for DDB2 and H3K9me3 at HIF1A promoter, DDB2 knockdown with HIF1α mRNA and angiogenic marker readout, xenograft tumor growth Oncogene Medium 31740787
2004 Four DDB2 splicing variants (D1-D4) were identified in HeLa cells; D1 and D2 act as dominant negative inhibitors of DNA repair; D1/D2 are not part of the damaged DNA-protein complex (EMSA); DDB2-WT interacts with D1 via co-immunoprecipitation; D1 expression reduces DDB1 nuclear import. RT-PCR, EMSA, DNA repair assay, co-immunoprecipitation, nuclear import assay Biochemical and biophysical research communications Medium 14751237
2001 DDB2 is required for nuclear accumulation of DDB1; DDB2 C-terminal deletion mutants that fail to bind DDB1 can still associate with HBx and enhance nuclear accumulation of HBx independently of DDB1 binding, revealing a DDB1-independent DDB2 function in nuclear import. DDB2 deletion mutant expression, co-immunoprecipitation, nuclear localization assay Journal of virology Medium 11581406
2008 DDB2 levels in the cell critically determine the amount of DDB1 temporally immobilized on UV-damaged DNA; DDB2 (not CUL4A) is indispensable for DDB1 binding to damage sites; UV-induced DDB2 proteolysis releases DDB1 from continuous association with unrepaired DNA. FRAP of fluorescently tagged DDB1, DDB2 knockdown/overexpression, local UV irradiation Molecular and cellular biology Medium 18936169
2000 Both DDB1 and DDB2 subunits must be present for UV-damaged DNA binding activity; XP-E patient-derived DDB2 mutations (L350P, ΔN349, others) abolish DDB activity when expressed in insect cells; wild-type p48 (DDB2) restores DDB activity to XP-E cell-free extracts; these mutations do not affect nuclear localization of p48. Baculovirus overexpression of individual subunits, EMSA with UV-damaged DNA, complementation of XP-E extracts The Journal of biological chemistry High 10777490

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2003 The ubiquitin ligase activity in the DDB2 and CSA complexes is differentially regulated by the COP9 signalosome in response to DNA damage. Cell 604 12732143
2008 Structural basis of UV DNA-damage recognition by the DDB1-DDB2 complex. Cell 353 19109893
2012 PARP1 promotes nucleotide excision repair through DDB2 stabilization and recruitment of ALC1. The Journal of cell biology 214 23045548
2003 In vivo recruitment of XPC to UV-induced cyclobutane pyrimidine dimers by the DDB2 gene product. The Journal of biological chemistry 198 12944386
1993 Comparative analysis of binding of human damaged DNA-binding protein (XPE) and Escherichia coli damage recognition protein (UvrA) to the major ultraviolet photoproducts: T[c,s]T, T[t,s]T, T[6-4]T, and T[Dewar]T. The Journal of biological chemistry 175 8407968
2001 The xeroderma pigmentosum group E gene product DDB2 is a specific target of cullin 4A in mammalian cells. Molecular and cellular biology 140 11564859
1995 Chromosomal localization and cDNA cloning of the genes (DDB1 and DDB2) for the p127 and p48 subunits of a human damage-specific DNA binding protein. Genomics 135 8530102
2002 p53 Binds and activates the xeroderma pigmentosum DDB2 gene in humans but not mice. Molecular and cellular biology 134 11971958
2006 Cullin 4A-mediated proteolysis of DDB2 protein at DNA damage sites regulates in vivo lesion recognition by XPC. The Journal of biological chemistry 129 16527807
2005 DDB1-DDB2 (xeroderma pigmentosum group E) protein complex recognizes a cyclobutane pyrimidine dimer, mismatches, apurinic/apyrimidinic sites, and compound lesions in DNA. The Journal of biological chemistry 129 16223728
2012 DDB2 promotes chromatin decondensation at UV-induced DNA damage. The Journal of cell biology 121 22492724
2000 Human damage-specific DNA-binding protein p48. Characterization of XPE mutations and regulation following UV irradiation. The Journal of biological chemistry 116 10777490
2014 Chromatin retention of DNA damage sensors DDB2 and XPC through loss of p97 segregase causes genotoxicity. Nature communications 97 24770583
2007 Differential sensitivity of malignant glioma cells to methylating and chloroethylating anticancer drugs: p53 determines the switch by regulating xpc, ddb2, and DNA double-strand breaks. Cancer research 96 18089819
2007 Dynamic in vivo interaction of DDB2 E3 ubiquitin ligase with UV-damaged DNA is independent of damage-recognition protein XPC. Journal of cell science 91 17635991
2004 UV radiation-induced XPC translocation within chromatin is mediated by damaged-DNA binding protein, DDB2. Carcinogenesis 91 14742321
2003 True XP group E patients have a defective UV-damaged DNA binding protein complex and mutations in DDB2 which reveal the functional domains of its p48 product. Human molecular genetics 90 12812979
2006 DNA damage binding protein component DDB1 participates in nucleotide excision repair through DDB2 DNA-binding and cullin 4A ubiquitin ligase activity. Cancer research 85 16951172
2004 DDB2 gene disruption leads to skin tumors and resistance to apoptosis after exposure to ultraviolet light but not a chemical carcinogen. Proceedings of the National Academy of Sciences of the United States of America 78 14769931
2009 DDB2 decides cell fate following DNA damage. Proceedings of the National Academy of Sciences of the United States of America 75 19541625
2003 The DDB2 nucleotide excision repair gene product p48 enhances global genomic repair in p53 deficient human fibroblasts. DNA repair 75 12826282
2005 Tumor-prone phenotype of the DDB2-deficient mice. Oncogene 74 15558025
2002 BRCA1 transcriptionally regulates damaged DNA binding protein (DDB2) in the DNA repair response following UV-irradiation. Cancer biology & therapy 70 12170778
2013 Malignant melanoma cells acquire resistance to DNA interstrand cross-linking chemotherapeutics by p53-triggered upregulation of DDB2/XPC-mediated DNA repair. Oncogene 68 23604128
2005 Enhanced DDB2 expression protects mice from carcinogenic effects of chronic UV-B irradiation. Cancer research 68 16288018
2003 Impaired regulation of tumor suppressor p53 caused by mutations in the xeroderma pigmentosum DDB2 gene: mutual regulatory interactions between p48(DDB2) and p53. Molecular and cellular biology 63 14560002
2013 NER initiation factors, DDB2 and XPC, regulate UV radiation response by recruiting ATR and ATM kinases to DNA damage sites. DNA repair 59 23422745
2005 DDB2, the xeroderma pigmentosum group E gene product, is directly ubiquitylated by Cullin 4A-based ubiquitin ligase complex. DNA repair 59 15811626
2013 DDB2 suppresses epithelial-to-mesenchymal transition in colon cancer. Cancer research 56 23610444
2002 Hepatitis B virus X protein associated with UV-DDB1 induces cell death in the nucleus and is functionally antagonized by UV-DDB2. The Journal of biological chemistry 56 12151405
2020 The deacetylase SIRT6 promotes the repair of UV-induced DNA damage by targeting DDB2. Nucleic acids research 53 32789493
2020 Ubiquitin and TFIIH-stimulated DDB2 dissociation drives DNA damage handover in nucleotide excision repair. Nature communications 53 32985517
2010 Overexpression of DDB2 enhances the sensitivity of human ovarian cancer cells to cisplatin by augmenting cellular apoptosis. International journal of cancer 53 20013802
2014 α-N-methylation of damaged DNA-binding protein 2 (DDB2) and its function in nucleotide excision repair. The Journal of biological chemistry 50 24753253
2010 DDB2 complex-mediated ubiquitylation around DNA damage is oppositely regulated by XPC and Ku and contributes to the recruitment of XPA. Molecular and cellular biology 49 20368362
2009 DDB2 (damaged-DNA binding protein 2) in nucleotide excision repair and DNA damage response. Cell cycle (Georgetown, Tex.) 49 19923893
1999 A newly identified patient with clinical xeroderma pigmentosum phenotype has a non-sense mutation in the DDB2 gene and incomplete repair in (6-4) photoproducts. The Journal of investigative dermatology 49 10469312
2008 The p38 mitogen-activated protein kinase augments nucleotide excision repair by mediating DDB2 degradation and chromatin relaxation. The Journal of biological chemistry 46 18806262
2015 Functional regulation of the DNA damage-recognition factor DDB2 by ubiquitination and interaction with xeroderma pigmentosum group C protein. Nucleic acids research 45 25628365
2015 DDB2 modulates TGF-β signal transduction in human ovarian cancer cells by downregulating NEDD4L. Nucleic acids research 45 26130719
2005 Xeroderma pigmentosum complementation group E protein (XPE/DDB2): purification of various complexes of XPE and analyses of their damaged DNA binding and putative DNA repair properties. Molecular and cellular biology 45 16260596
2020 EZH2 has a non-catalytic and PRC2-independent role in stabilizing DDB2 to promote nucleotide excision repair. Oncogene 43 32457468
2007 The xeroderma pigmentosum group E gene product DDB2 activates nucleotide excision repair by regulating the level of p21Waf1/Cip1. Molecular and cellular biology 43 17967871
2014 DDB2 suppresses tumorigenicity by limiting the cancer stem cell population in ovarian cancer. Molecular cancer research : MCR 41 24574518
2012 The deubiquitinating protein USP24 interacts with DDB2 and regulates DDB2 stability. Cell cycle (Georgetown, Tex.) 41 23159851
2013 DDB2: a novel regulator of NF-κB and breast tumor invasion. Cancer research 40 23774208
2003 Basal transcriptional regulation of human damage-specific DNA-binding protein genes DDB1 and DDB2 by Sp1, E2F, N-myc and NF1 elements. Nucleic acids research 39 12527763
2001 DDB2 induces nuclear accumulation of the hepatitis B virus X protein independently of binding to DDB1. Journal of virology 38 11581406
2016 Autophagic UVRAG Promotes UV-Induced Photolesion Repair by Activation of the CRL4(DDB2) E3 Ligase. Molecular cell 36 27203177
2019 Emerging Roles of DDB2 in Cancer. International journal of molecular sciences 33 31635251
2010 DDB2, an essential mediator of premature senescence. Molecular and cellular biology 33 20351176
2012 MC1R variant allele effects on UVR-induced phosphorylation of p38, p53, and DDB2 repair protein responses in melanocytic cells in culture. The Journal of investigative dermatology 32 22336944
2005 Cross-resistance to death ligand-induced apoptosis in cisplatin-selected HeLa cells associated with overexpression of DDB2 and subsequent induction of cFLIP. Molecular pharmacology 32 15644494
2008 Cellular concentrations of DDB2 regulate dynamic binding of DDB1 at UV-induced DNA damage. Molecular and cellular biology 31 18936169
2007 Ddb2 is a haploinsufficient tumor suppressor and controls spontaneous germ cell apoptosis. Human molecular genetics 30 17468495
2018 DDB2 represses ovarian cancer cell dedifferentiation by suppressing ALDH1A1. Cell death & disease 29 29752431
2010 Antimony impairs nucleotide excision repair: XPA and XPE as potential molecular targets. Chemical research in toxicology 29 20509621
2011 p21 cooperates with DDB2 protein in suppression of ultraviolet ray-induced skin malignancies. The Journal of biological chemistry 28 22167187
2017 NRIP/DCAF6 stabilizes the androgen receptor protein by displacing DDB2 from the CUL4A-DDB1 E3 ligase complex in prostate cancer. Oncotarget 26 28212551
2006 E2F regulates DDB2: consequences for DNA repair in Rb-deficient cells. Oncogene 26 17173070
2017 DDB2 Is a Novel Regulator of Wnt Signaling in Colon Cancer. Cancer research 25 29021137
2015 DDB2 is involved in ubiquitination and degradation of PAQR3 and regulates tumorigenesis of gastric cancer cells. The Biochemical journal 25 26205499
2000 Studies of the murine DDB1 and DDB2 genes. Gene 25 10713455
2022 Hypoxia-inducible CircPFKFB4 Promotes Breast Cancer Progression by Facilitating the CRL4DDB2 E3 Ubiquitin Ligase-mediated p27 Degradation. International journal of biological sciences 23 35813480
2006 Evaluation of xeroderma pigmentosum XPA, XPC, XPD, XPF, XPB, XPG and DDB2 genes in familial early-onset lung cancer predisposition. International journal of cancer 22 16550608
2018 DDB2 regulates Epithelial-to-Mesenchymal Transition (EMT) in Oral/Head and Neck Squamous Cell Carcinoma. Oncotarget 20 30410671
2012 DDB2 is a novel AR interacting protein and mediates AR ubiquitination/degradation. The international journal of biochemistry & cell biology 20 22846800
2013 DDB2 association with PCNA is required for its degradation after UV-induced DNA damage. Cell cycle (Georgetown, Tex.) 19 24200966
2006 Polymorphisms in DNA damage binding protein 2 (DDB2) and susceptibility of primary lung cancer in the Chinese: a case-control study. Carcinogenesis 19 16522664
2021 ERα determines the chemo-resistant function of mutant p53 involving the switch between lincRNA-p21 and DDB2 expressions. Molecular therapy. Nucleic acids 18 34589276
2006 Role of Claspin in regulation of nucleotide excision repair factor DDB2. DNA repair 18 17196446
2017 UV radiation-induced SUMOylation of DDB2 regulates nucleotide excision repair. Carcinogenesis 16 28981631
2017 Whole Exome Sequencing allows the identification of two novel groups of Xeroderma pigmentosum in Tunisia, XP-D and XP-E: Impact on molecular diagnosis. Journal of dermatological science 16 29169765
2004 Human DDB2 splicing variants are dominant negative inhibitors of UV-damaged DNA repair. Biochemical and biophysical research communications 16 14751237
2022 Targeted CUL4A inhibition synergizes with cisplatin to yield long-term survival in models of head and neck squamous cell carcinoma through a DDB2-mediated mechanism. Cell death & disease 15 35428778
2021 DDB2 regulates DNA replication through PCNA-independent degradation of CDT2. Cell & bioscience 15 33557942
2019 NER-factor DDB2 regulates HIF1α and hypoxia-response genes in HNSCC. Oncogene 15 31740787
2016 DDB2 increases radioresistance of NSCLC cells by enhancing DNA damage responses. Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine 15 27553023
2005 Xeroderma pigmentosum group E and DDB2, a smaller subunit of damage-specific DNA binding protein: proposed classification of xeroderma pigmentosum, Cockayne syndrome, and ultraviolet-sensitive syndrome. Journal of dermatological science 15 16325378
2019 Regulation of liver receptor homologue-1 by DDB2 E3 ligase activity is critical for hepatic glucose metabolism. Scientific reports 14 30923324
2017 Dual control of ROS1-mediated active DNA demethylation by DNA damage-binding protein 2 (DDB2). The Plant journal : for cell and molecular biology 13 29078035
2015 Combination of Aβ Secretion and Oxidative Stress in an Alzheimer-Like Cell Line Leads to the Over-Expression of the Nucleotide Excision Repair Proteins DDB2 and XPC. International journal of molecular sciences 13 26263968
2013 A novel DDB2-ATM feedback loop regulates human cytomegalovirus replication. Journal of virology 13 24335308
2012 Tumor regression by phenethyl isothiocyanate involves DDB2. Cancer biology & therapy 13 23114715
2011 Nucleotide excision repair proteins rapidly accumulate but fail to persist in human XP-E (DDB2 mutant) cells. Photochemistry and photobiology 12 21388382
2002 Restoration of UV sensitivity in UV-resistant HeLa cells by antisense-mediated depletion of damaged DNA-binding protein 2 (DDB2). FEBS letters 12 11852074
2022 DDB2 represses epithelial-to-mesenchymal transition and sensitizes pancreatic ductal adenocarcinoma cells to chemotherapy. Frontiers in oncology 11 36568213
2021 USP44 Stabilizes DDB2 to Facilitate Nucleotide Excision Repair and Prevent Tumors. Frontiers in cell and developmental biology 11 33937266
2016 DDB2 (damaged-DNA binding 2) protein: a new modulator of nanomechanical properties and cell adhesion of breast cancer cells. Nanoscale 11 26879405
2015 The 5'-UTR of DDB2 harbors an IRES element and upregulates translation during stress conditions. Gene 11 26187069
2013 Coordination between p21 and DDB2 in the cellular response to UV radiation. PloS one 11 24260342
2023 MBD2 facilitates tumor metastasis by mitigating DDB2 expression. Cell death & disease 10 37142578
2016 Chromatin association of XRCC5/6 in the absence of DNA damage depends on the XPE gene product DDB2. Molecular biology of the cell 10 28035050
2015 Variants in SELL, MRPS36P2, TP63, DDB2, CACNA1H, ADAM19, GNAI1, CDH13 and GABRG2 interact to confer risk of acne in Chinese population. The Journal of dermatology 10 25573302
2013 SUMOylation of damaged DNA-binding protein DDB2. Biochemical and biophysical research communications 10 23860269
2007 DDB2-independent role for p53 in the recovery from ultraviolet light-induced replication arrest. Cell cycle (Georgetown, Tex.) 10 17630510
2021 Regulation of ddb2 expression in blind cavefish and zebrafish reveals plasticity in the control of sunlight-induced DNA damage repair. PLoS genetics 9 33544716
2021 MEKK1-Dependent Activation of the CRL4 Complex Is Important for DNA Damage-Induced Degradation of p21 and DDB2 and Cell Survival. Molecular and cellular biology 9 34251884
2014 Monitoring repair of UV-induced 6-4-photoproducts with a purified DDB2 protein complex. PloS one 9 24489677
2010 Detection of bulky DNA lesions: DDB2 at the interface of chromatin and DNA repair in eukaryotes. IUBMB life 9 21117171

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