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Showing ERCC1 — RAD10 is a alias.

ERCC1

DNA excision repair protein ERCC-1 · UniProt P07992

Length
297 aa
Mass
32.6 kDa
Annotated
2026-06-09
100 papers in source corpus 46 papers cited in narrative 46 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 10/10 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

ERCC1 is the obligate non-catalytic partner subunit of the ERCC1-XPF structure-specific endonuclease, a heterodimer that incises duplex DNA on the 5' side of duplex/single-strand junctions and thereby executes the 5' incision step of nucleotide excision repair (NER) and a broad set of related DNA-processing reactions (PMID:8253090, PMID:7559382, PMID:9525876). The protein was first cloned by complementation of repair-deficient CHO cells and recognized as the homolog of yeast RAD10, whose product is a single-stranded-DNA-binding protein required for the incision step of NER (PMID:2420469, PMID:3912171, PMID:1741062). ERCC1/RAD10 functions only in stable 1:1 complex with XPF/RAD1, an interaction mediated by conserved C-terminal regions and required for both nuclease activity and complex assembly; the two subunits are mutually dependent for stability in mammalian cells (PMID:1518857, PMID:8253764, PMID:11160918). The reconstituted complex cleaves stem-loop, splayed-arm, bubble and flap substrates at the 5' side of the junction, requiring divalent cations and a minimum of 4-8 unpaired nucleotides, and cooperates with XPG to perform the dual incision of NER (PMID:7559571, PMID:9525876). Multiple DNA-binding domains, including the ERCC1 HhH domain and the XPF nuclease domain, act cooperatively, and distinct interaction surfaces separate NER from non-NER activities (PMID:22547097, PMID:29795289). Recruitment to damage is governed by ERCC1's interactions with XPA and RPA, which form a sequential ternary RPA-XPA-ERCC1 complex that loads the incision complex onto lesions, while ERCC1 stability and translocation to UV-damage foci depend on deubiquitylation by USP45 (PMID:8197174, PMID:8972858, PMID:25538220). Beyond NER, ERCC1-XPF removes 3' non-homologous tails during single-strand annealing and recombination through scaffolds such as Saw1/SLX4 (the latter regulated by Mec1/Tel1 phosphorylation), unhooks interstrand crosslinks in cooperation with SLX4/FANCP downstream of FANCD2 monoubiquitination, processes 3'-blocked oxidative and Top1-derived strand breaks, and participates in double-strand break repair (PMID:7891718, PMID:18471978, PMID:19805513, PMID:20382573, PMID:24726325, PMID:15371342, PMID:18541667). Non-repair roles include silencing of imprinted genes through CTCF/cohesin/ATRX, resolution of R-loops via the splicing factor XAB2, and modulation of hRad52 recombination activity (PMID:28368372, PMID:34039990, PMID:14734547). ERCC1 also has an XPF-independent function in mitotic progression and cytokinesis (PMID:21839691). The ERCC1 R156W mutation, which destabilizes ERCC1 and XPF and impairs damage recruitment, causes a human NER/crosslink-repair-deficiency disorder (PMID:33315086).

Mechanistic history

Synthesis pass · year-by-year structured walk · 10 steps
  1. 1986 High

    Establishing the molecular identity of the human repair gene: cloning ERCC1 and recognizing its homology to yeast RAD10 created the framework for understanding it as a conserved NER factor.

    Evidence cDNA cloning and complementation of UV/mitomycin-C-sensitive CHO mutants, with sequence comparison to RAD10

    PMID:2420469 PMID:3912171

    Open questions at the time
    • Cloning alone did not define the biochemical activity or partner of ERCC1
    • The functional transcript was identified but the protein's enzymatic role was unknown
  2. 1992 High

    Defining the functional unit: RAD1-RAD10 (XPF-ERCC1) forms an obligate, salt-resistant complex that is itself a single-stranded-DNA endonuclease, answering whether the subunits act alone or together.

    Evidence Reciprocal Co-IP in vivo and in vitro, interaction-defective mutants, purified-protein endonuclease assays in yeast

    PMID:1518857 PMID:1741062 PMID:8479526

    Open questions at the time
    • Did not yet define the precise junction geometry of cleavage
    • Substrate range beyond ssDNA was unresolved
  3. 1995 High

    Placing the activity in NER mechanistically: the complex incises at the 5' side of bubble structures and, with XPG, reconstitutes the dual incision of NER, resolving which incision the complex performs.

    Evidence Native HeLa complex purification, in vitro incision/dual-incision assays on bubble substrates, RPA stimulation

    PMID:7559382 PMID:7559571 PMID:8253090

    Open questions at the time
    • Did not explain how the complex is targeted to lesions in cells
    • Ruled out Holliday junction resolution but left recombination intermediate roles open
  4. 1996 High

    Defining damage targeting: ERCC1 and RPA bind distinct regions of XPA to form a sequential RPA-XPA-ERCC1 ternary complex, explaining how the incision nuclease is recruited to lesions.

    Evidence Yeast two-hybrid, recombinant binding, SPR affinity measurements and domain mapping

    PMID:8197174 PMID:8972858

    Open questions at the time
    • Did not establish the in vivo order of assembly at chromatin lesions
    • Regulation of recruitment by post-translational modification was unaddressed
  5. 1998 High

    Generalizing substrate specificity: purified recombinant ERCC1-XPF cleaves diverse junction substrates 5' of the junction with defined cation and unpaired-nucleotide requirements, establishing it as a general structure-specific endonuclease.

    Evidence In vitro endonuclease assays on stem-loop, splayed-arm and flap substrates with purified recombinant complex

    PMID:9525876

    Open questions at the time
    • Did not connect each in vitro substrate to a specific in vivo pathway
    • Cofactor requirements in cells were not defined
  6. 2004 High

    Expanding pathway scope: genetic and biochemical work showed Rad1-Rad10/ERCC1-XPF processes recombination intermediates, removes 3'-blocked termini from oxidative breaks, and modulates hRad52, defining non-NER DNA-processing roles.

    Evidence Yeast epistasis and synthetic lethality, in vitro cleavage of 3'-phosphoglycolate substrates, Co-IP and functional assays with hRad52

    PMID:12032096 PMID:12368472 PMID:14706347 PMID:14734547 PMID:15371342 PMID:7891718

    Open questions at the time
    • Recruitment factors for non-NER substrates were not yet identified
    • Whether these roles were direct nuclease functions or scaffolding was not always resolved
  7. 2010 High

    Identifying recruitment scaffolds for recombination/SSA: Saw1 and Slx4 target Rad1-Rad10 to 3' tails, with Mec1/Tel1 phosphorylation of Slx4 licensing cleavage, defining how the nuclease is directed to recombination intermediates.

    Evidence Genetic screen, ChIP, physical interaction mapping, SSA assays and phosphosite mutagenesis in yeast

    PMID:18471978 PMID:20382573 PMID:23299942

    Open questions at the time
    • The mammalian equivalents of all scaffold interactions were not fully mapped
    • How phosphorylation activates cleavage mechanistically was unresolved
  8. 2014 High

    Integrating into the Fanconi/ICL pathway and defining its regulation: XPF-ERCC1 cooperates with SLX4/FANCP for ICL unhooking downstream of FANCD2 monoubiquitination, and USP45 deubiquitylation controls ERCC1 stability and damage localization.

    Evidence Xenopus egg-extract replication-coupled ICL repair with immunodepletion; FANCD2 chromatin/foci assays; in vitro deubiquitylation and USP45 knockout cells

    PMID:19805513 PMID:24726325 PMID:25538220

    Open questions at the time
    • The catalytic step of unhooking versus scaffold recruitment was not fully separated
    • Other regulatory modifications of ERCC1 were not characterized
  9. 2018 High

    Separating NER from non-NER functions genetically: mutations disrupting XPF-Rpa1 interactions abolish ICL repair and recombination while preserving NER, proving distinct interaction surfaces drive distinct pathways.

    Evidence Separation-of-function site-directed mutagenesis with NER, SSA and ICLR assays in yeast and human cells

    PMID:22547097 PMID:29795289

    Open questions at the time
    • Full structural basis for each interaction surface was not resolved
    • How cells partition the complex between pathways was unaddressed
  10. 2021 High

    Establishing non-repair functions and disease relevance: ERCC1-XPF silences imprinted genes via CTCF/cohesin/ATRX and resolves R-loops via XAB2, while the R156W mutation links ERCC1 destabilization to a human repair-deficiency disorder.

    Evidence In vivo biotinylation tagging, ChIP and KO mice for imprinting/R-loops; patient-derived and knock-in cells with NER and crosslinker assays

    PMID:28368372 PMID:33315086 PMID:34039990

    Open questions at the time
    • Whether the imprinting and R-loop roles require nuclease activity is unclear
    • The mechanistic basis of the XPF-independent mitotic role of ERCC1 is undefined

Open questions

Synthesis pass · forward-looking unresolved questions
  • It remains unresolved how ERCC1 executes its XPF-independent role in mitotic progression and cytokinesis, and how the complex is partitioned among its many repair and non-repair functions in cells.
  • No molecular partner identified for the XPF-independent mitotic function of ERCC1
  • No structural model integrating NER, ICL and recombination interaction surfaces

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140097 catalytic activity, acting on DNA 7 GO:0016787 hydrolase activity 4 GO:0003677 DNA binding 3 GO:0060090 molecular adaptor activity 3
Localization
GO:0005634 nucleus 3 GO:0000228 nuclear chromosome 2
Pathway
R-HSA-73894 DNA Repair 6 R-HSA-74160 Gene expression (Transcription) 2
Partners
HRAD52MSH2RPASLX4USP45XAB2XPAXPF
Complex memberships
ERCC1-XPF endonucleaseRPA-XPA-ERCC1 ternary complexSLX4-XPF-ERCC1XAB2-ERCC1-XPF-XPG

Evidence

Reading pass · 46 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1986 ERCC1 cDNA was cloned and found to encode a 297-amino acid protein; only the larger 1.1 kb transcript (not the alternatively spliced shorter form) could confer UV and mitomycin-C resistance to repair-deficient CHO cells. Significant amino acid sequence homology was found between ERCC1 and the yeast excision repair protein RAD10, particularly in a region with structural similarity to DNA-binding domains. DNA-mediated gene transfer, cDNA cloning, sequence analysis, complementation assay in UV-sensitive CHO mutant 43-3B Cell High 2420469
1985 The yeast RAD10 gene (ortholog of ERCC1) is required for the incision step of nucleotide excision repair of UV-damaged DNA. A genomic deletion of RAD10 does not affect viability but causes high UV sensitivity. Genetic complementation (transformation of rad10 mutants), nucleotide sequencing, UV sensitivity assay The EMBO journal High 3912171
1990 RAD10 protein was purified from yeast and shown to be a DNA-binding protein with strong preference for single-stranded DNA. RAD10 promotes renaturation (annealing) of complementary DNA strands. Protein purification, DNA-binding assay, strand annealing assay Nature High 1741062
1990 RAD10 is required for mitotic recombination in yeast; the rad10 deletion reduced intrachromosomal recombination at direct repeats and lowered efficiency of homologous integration of linear DNA. RAD1 and RAD10 function together in the same recombination pathway, distinct from the RAD52 pathway. Genetic epistasis analysis, recombination frequency assay in yeast deletion mutants Molecular and cellular biology High 2188090
1992 RAD1 and RAD10 proteins form a stable, specific complex in vivo (shown by co-immunoprecipitation) and in vitro. The interaction is mediated by C-terminal regions of both proteins, is resistant to 1 M NaCl and low SDS, and is essential for DNA repair and recombination activities (a rad1 mutant defective in RAD10 binding is also defective in repair and recombination). Co-immunoprecipitation from yeast cell extracts, in vitro co-IP, hydroxylamine mutagenesis to identify interaction-defective mutant Proceedings of the National Academy of Sciences of the United States of America High 1518857
1992 The RAD1-RAD10 complex constitutes a single-stranded DNA endonuclease; purified Rad1 and Rad10 together specifically degrade single-stranded DNA by an endonucleolytic mechanism. Protein purification, in vitro endonuclease assay on single-stranded DNA substrates Nature High 8479526
1993 ERCC1 co-corrects NER defects of rodent group 1, group 4, and XP-F cell extracts; group 1-correcting activity has a native molecular mass of ~100 kDa and contains the 33 kDa ERCC1 polypeptide together with XPF/ERCC4 correcting activity, establishing that ERCC1 exists as a functional heterodimeric complex with XPF. In vitro NER reconstitution, biochemical fractionation, immunoblotting, complementation of cell-free extracts The EMBO journal High 8253090
1993 Rad1-Rad10 complex forms in the yeast cell nucleus; the Rad10-binding domain of Rad1 maps to amino acids 809-997, and the Rad1-binding domain of Rad10 maps to amino acids 90-210. These domains are hydrophobic and evolutionarily conserved. No interaction was detected between human ERCC1 and yeast Rad1. Two-hybrid system (in vivo nuclear interaction), domain mapping Molecular microbiology Medium 8361362
1993 Purified Rad1/Rad10 complex has endonuclease activity on single-stranded DNA (preferentially) and negatively supercoiled double-stranded DNA; it produces 3'-OH and 5'-phosphate termini. The complex lacks exonuclease activity and does not preferentially cleave UV-irradiated DNA. Rad1 and Rad10 associate in a 1:1 stoichiometric complex of ~190 kDa. Protein purification, in vitro endonuclease assay, substrate specificity analysis The Journal of biological chemistry High 8253764
1994 XPA and ERCC1 specifically interact both in vivo (two-hybrid system) and in vitro (with recombinant proteins). Initial domain mapping identified regions in ERCC1 and XPA mediating this interaction, suggesting XPA may recruit the ERCC1-containing incision complex to damaged DNA. Yeast two-hybrid assay, in vitro binding with recombinant proteins, domain mapping Proceedings of the National Academy of Sciences of the United States of America High 8197174
1994 Purified Rad1-Rad10 cleaves model recombination and repair intermediates at duplex-single-strand junctions, specifically on the strand containing the 3' single-stranded tail, establishing that the complex incises DNA 5' to damaged bases during NER and cleaves specific recombination intermediates. In vitro endonuclease assay on model recombination and repair intermediate substrates with purified proteins Science High 8091230
1995 The XPF-ERCC1 heterodimer was purified from HeLa cells; it contains ERCC1 (38 kDa) and XPF (112 kDa), complementing NER defects in ERCC-1, ERCC-4, and XP-F cell-free extracts. The complex has endonuclease activity preferring single-stranded DNA and the single-stranded bubble region of duplex DNA; nicking of supercoiled DNA is stimulated by RPA in the presence of UV damage. Protein purification from HeLa cells, NER complementation assay, endonuclease activity assay, RPA stimulation assay The Journal of biological chemistry High 7559382
1995 RAD1 and RAD10 are uniquely required among NER genes for double-strand break-induced recombination; only rad1 and rad10 deletions (not rad2, rad3, rad14, rad7, rad16 mutations) caused ~20-fold reduction in gap repair and single-strand annealing at HO-induced DSBs, establishing a specific role for the Rad1-Rad10 complex in removing nonhomologous sequences from DSB ends. Genetic epistasis with HO endonuclease-induced DSBs, recombination frequency measurement in yeast deletion mutants Molecular and cellular biology High 7891718
1995 Purified Rad1-Rad10 incises bubble structure DNA at the 5' side of the unpaired region. When co-incubated with XPG, incisions occurred at both sides of the bubble, reconstituting the dual incision step of NER. Rad1-Rad10 was unable to resolve synthetic Holliday junctions (negative finding regarding previously proposed junction resolution activity). In vitro incision assay with purified Rad1-Rad10 and XPG on synthetic bubble substrates The Journal of biological chemistry High 7559571
1996 MSH2 and MSH3 mismatch repair proteins function in the RAD1-RAD10 recombination pathway; msh3 mutations have an effect on recombination similar to rad1/rad10 mutations, and epistasis analysis places MSH2 and MSH3 in the RAD1-RAD10 pathway of mitotic recombination. Genetic epistasis analysis, recombination frequency measurement in yeast deletion mutants Genetics Medium 8849883
1996 RPA and ERCC1 both bind to distinct, non-overlapping regions of XPA and can form a ternary RPA-XPA-ERCC1 complex in vitro. The KD of RPA for XPA is 1.9×10⁻⁸ M and of ERCC1 for XPA is 2.5×10⁻⁷ M. RPA binds XPA first (sequentially) and facilitates subsequent ERCC1 binding. In vitro binding assays, surface plasmon resonance, domain mapping, ternary complex detection Nucleic acids research High 8972858
1998 Recombinant ERCC1-XPF purified from insect cells cleaves stem-loop, splayed arm, and flap substrates at duplex-single-strand junctions, removing 3' protruding single-stranded arms; cleavage requires divalent cations (optimal in 0.2 mM Mn²⁺), a minimum of 4-8 unpaired nucleotides, and a single-stranded arm (3' or 5'). All incisions occur in the duplex strand at the 5' side of the junction, 2-8 nt from the junction, independent of other proteins (e.g., RPA). In vitro endonuclease assay with purified recombinant ERCC1-XPF on defined substrate structures, divalent cation requirement analysis The Journal of biological chemistry High 9525876
2001 ERCC1 and XPF are mutually dependent for stability in mammalian cells. Separately produced ERCC1 and XPF can reconstitute functional ERCC1-XPF when combined, establishing that the individual subunits can fold independently. ERCC1 alone showed partial NER repair activity in ERCC1-defective extracts due to trace XPF present. ERCC1 lacking the first 88 amino acids retained function. Sequence comparison revealed homology between the C-terminal regions of ERCC1 and XPF, suggesting an ancient gene duplication. Recombinant protein expression in E. coli, NER complementation assay with cell-free extracts, immunoassay for XPF levels Nucleic acids research High 11160918
2002 Rad1-Rad10 (ERCC1-XPF ortholog) and Tdp1 function as redundant primary pathways for repair of Top1 replication damage in yeast; tdp1 rad1 double mutants are highly sensitive to camptothecin and show a TOP1-dependent growth defect. Both pathways feed into RAD52/RAD51/RAD50-dependent recombination equally. The Rad1-Rad10 pathway also requires RAD59 and SRS2 and is independent of other NER genes. Genetic epistasis analysis, camptothecin sensitivity assay, synthetic lethality analysis in yeast deletion mutants Proceedings of the National Academy of Sciences of the United States of America High 12368472
2002 Endogenous DNA abasic sites cause synthetic lethality in yeast lacking Apn1, Apn2, and Rad1/Rad10 (or Rad1), establishing that Rad1-Rad10 processes 3'-blocked single-strand breaks arising from abasic site processing under physiological conditions. Genetic synthetic lethality analysis, bacterial complementation (Nfo expression), epistasis with DNA glycosylase mutants The EMBO journal High 12032096
2004 Rad1-Rad10 nuclease is required for removal of 3'-blocked termini from oxidative DNA strand breaks; yeast Rad1-Rad10 nuclease cleaves DNA with a 3'-phosphoglycolate terminus, and three pathways (Apn1, Apn2, Rad1-Rad10) remove 3'-blocked termini from H₂O₂-induced strand breaks. In vitro nuclease assay on 3'-phosphoglycolate-terminated substrate, genetic epistasis in yeast deletion mutants, H₂O₂ sensitivity assay Genes & development High 15371342
2004 XPF/ERCC1 is stably associated with hRad52 in human cell-free extracts; the interaction is direct, mediated by the N-terminal domain of hRad52 and XPF. Complex formation stimulates XPF/ERCC1 endonuclease activity and simultaneously attenuates hRad52 strand annealing activity. Co-immunoprecipitation from cell-free extracts, direct binding assay with recombinant proteins, domain mapping, endonuclease activity assay, strand annealing assay The Journal of biological chemistry High 14734547
2004 ERCC1 physically interacts with MSH2 complexes in HeLa cell extracts, and suppression of ERCC1 increases sensitivity to cisplatin (but not UV) in XPA-deficient cells in an MSH2-dependent manner, establishing a co-operative role of ERCC1 and MSH2 in cisplatin ICL resistance independent of NER. The ERCC1 region required for MSH2 co-immunoprecipitation maps to amino acids 184-260, overlapping with the XPF-binding domain. RNA interference, co-immunoprecipitation from HeLa extracts, domain mapping by tagged ERCC1, cisplatin sensitivity assay in XPA-deficient cells DNA repair High 14706347
2008 ERCC1-XPF endonuclease is required for DSB repair in mammals; ERCC1-XPF-deficient fibroblasts are hypersensitive to gamma irradiation with persistent γH2AX foci. In vitro DSB repair of substrates with 3' overhangs generates large deletions in the absence of ERCC1-XPF. Ercc1⁻/⁻ Ku86⁻/⁻ double mutant fibroblasts are more sensitive to irradiation than single mutants, indicating ERCC1-XPF participates in a Ku86-independent end-joining pathway. Gamma irradiation sensitivity assay, γH2AX foci analysis, in vitro DSB repair assay, mouse epistasis genetics (Ercc1/Ku86 double mutant) Molecular and cellular biology High 18541667
2008 ERCC1/XPF limits LINE-1 retrotransposition; reduction of XPF in human cells increased retrotransposition, and complementation of ERCC1-deficiency in hamster cells reduced retrotransposition, establishing that the ERCC1-XPF heterodimer processes flap intermediates generated during LINE-1 retrotransposition. siRNA knockdown, genetic complementation of ERCC1-deficient hamster cells, retrotransposition reporter assay DNA repair Medium 18396111
2008 Saw1 protein was identified as required for Rad1/Rad10-dependent processing of recombination intermediates in SSA; Saw1 physically interacts with Rad1/Rad10, Msh2/Msh3, and Rad52, and saw1 mutants defective in Rad1 interaction (but retaining Rad52/Msh2 interaction) are defective in 3' flap removal. Deletion of SAW1 abolished Rad1 association at SSA intermediates in vivo. Microarray-based genetic screen, physical interaction assays, ChIP, SSA assay in yeast Molecular cell High 18471978
2009 XPF-ERCC1 is required for ICL unhooking and for stable localization of monoubiquitinated FANCD2 to chromatin at ICL sites; in XPF-ERCC1-deficient cells, FANCD2 monoubiquitination occurs but its chromatin association is dramatically reduced and ICL-induced FANCD2 foci are significantly lower, establishing that ICL unhooking by XPF-ERCC1 is necessary for FA pathway activation and subsequent HR-mediated DSB repair. FANCD2 monoubiquitination assay, chromatin fractionation, immunofluorescence foci analysis in Ercc1⁻/⁻ and XPF-deficient cells Molecular and cellular biology High 19805513
2010 Mec1/Tel1-dependent phosphorylation of Slx4 at Thr113 is required for efficient cleavage of 3' non-homologous DNA tails by Rad1-Rad10 during SSA and HR. Slx4 is recruited to 3' NH tails during DSB repair independently of its phosphorylation, but phosphorylation is required for Rad1-Rad10 cleavage activity at these sites. DSB repair assay, phosphorylation site mutagenesis, ChIP, epistasis with mec1/tel1 mutants in yeast DNA repair High 20382573
2012 Multiple DNA binding domains of ERCC1-XPF cooperate for NER activity; mutations in the HhH domain of ERCC1 and the nuclease domain of XPF abolish cleavage on model substrates. Mutations in multiple binding domains are needed to diminish NER activity, suggesting protein-protein interactions in the NER incision complex compensate for individual DNA binding defects. ICL repair requires tighter substrate binding than NER (more sensitive to DNA-binding mutations). In vitro cleavage assay on model substrates, NER activity assay in cell extracts and in vivo with domain mutants, mitomycin C and UV sensitivity assay The Journal of biological chemistry High 22547097
2012 Rad1-Rad10 nuclease promotes formation of crossover recombinants between dispersed repeat sequences (ectopic sequences); all three nucleases (Rad1-Rad10, Mus81-Mms4, Yen1) participate in processing recombination intermediates between dispersed repeats, and Rad1-Rad10 promotes crossovers via a mechanism involving clipping and subsequent resolution of a Holliday junction-containing intermediate. Genetic analysis in yeast deletion mutants, measurement of crossover and noncrossover recombinants, detection of joint molecule intermediates Nature structural & molecular biology Medium 22885325
2013 Saw1 is a structure-specific DNA binding protein with high affinity for splayed arm and 3'-flap DNAs; Saw1 directly interacts with Rad1 to facilitate targeting of Rad1/Rad10 to 3'-tailed substrates in vivo and in vitro, and enhances 3'-tail cleavage by Rad1/Rad10 in a purified system. The order of assembly is: Saw1 (structure-specific DNA binding) → recruits Rad1/Rad10 → cleavage of 3' tails. Purified protein DNA-binding assay, in vitro cleavage assay with purified proteins, ChIP, physical interaction assay The EMBO journal High 23299942
2013 Only one of four ERCC1 protein isoforms (the full-length isoform) has full capacity for nucleotide excision repair and cisplatin resistance; none of the 16 commercially available ERCC1 antibodies (including 8F1) can distinguish among the four isoforms, limiting their diagnostic utility. NER functional assay for each isoform, cisplatin resistance assay, antibody epitope mapping for 16 antibodies The New England journal of medicine High 23514287
2013 Small molecule NSC 130813 disrupts the ERCC1-XPF protein-protein interaction in cells and synergizes with cisplatin and mitomycin C; the compound binds directly to the XPF domain responsible for ERCC1 interaction (demonstrated by Biacore surface plasmon resonance), increases UV-mediated cytotoxicity, and modifies DNA repair (γH2AX staining). Virtual screening, Biacore binding assay, proximity ligation assay, cytotoxicity assay, γH2AX analysis Molecular pharmacology Medium 23580445
2014 XPF-ERCC1 cooperates with SLX4/FANCP to perform unhooking incisions during replication-coupled ICL repair in Xenopus egg extracts; efficient recruitment of XPF-ERCC1 and SLX4 to the ICL depends on FANCD2 monoubiquitination. Xenopus egg extract ICL repair assay, immunodepletion, recruitment assay at ICL sites Molecular cell High 24726325
2014 USP45 deubiquitylase associates with ERCC1 via a short acidic motif outside the USP45 catalytic domain, deubiquitylates ERCC1 in vitro, and is required for ERCC1 translocation to UV-damage-induced subnuclear foci. USP45 knockout cells have elevated ubiquitylated ERCC1, are hypersensitive to UV and ICL agents (similar to ERCC1-deficient cells), and show reduced UV-induced DNA damage repair. Co-immunoprecipitation, in vitro deubiquitylation assay, USP45 knockout cells, immunofluorescence foci assay, UV/ICL sensitivity assay The EMBO journal High 25538220
2014 EGFR and ERCC1 interact upon ionizing radiation (IR)-induced DNA damage; this interaction was identified by mass spectrometry of the EGFR interactome, validated biochemically and by proximity ligation assay. Depletion of ERCC1 or EGFR impairs IR-induced DNA repair (comet assay, γH2AX foci), and this EGFR-dependent repair pathway operates independently of DNA-PKcs. Mass spectrometry of EGFR interactome, biochemical co-immunoprecipitation, proximity ligation assay, siRNA knockdown, comet assay, γH2AX foci analysis in DNAPKcs-deficient cells Clinical cancer research Medium 24780295
2015 ERCC1-XPF participates in repair of Top1-attached nick DNA lesions; ERCC1-XPF shows nuclease activity on 3'-phosphotyrosyl bond nick-containing DNA in the presence of RPA. ERCC1-XPF and RPA form a DNA-protein complex on nick DNA substrates in vitro, co-localize in camptothecin-treated cells, and DNA repair synthesis of Tyr-nick DNA lesions occurs with NER factors including ERCC1-XPF. In vitro nuclease assay on Tyr-nick DNA substrate, electrophoretic mobility shift assay, co-localization by immunofluorescence, in vitro repair synthesis assay Carcinogenesis Medium 26025908
2017 ERCC1-XPF complex interacts with the insulator binding protein CTCF, cohesin subunits SMC1A and SMC3, and MBD2 in mouse liver nuclei; ERCC1-XPF co-localizes with ATRX at promoters and imprinting control regions (ICRs) of imprinted genes during postnatal hepatic development. Loss of Ercc1 or DNA crosslink damage triggers CTCF localization to heterochromatin, dissociation of CTCF-cohesin and ATRX from ICRs, altered histone marks, and aberrant developmental expression of imprinted genes without altering DNA methylation. In vivo biotinylation tagging in mice, co-immunoprecipitation, ChIP, gene expression analysis in Ercc1 knockout and MMC-treated mice Nature cell biology High 28368372
2018 Two rad1 mutations that disrupt XPF-Rpa1 interactions selectively disable non-NER functions (ICL repair, direct repeat recombination) while retaining UV lesion repair activity; analogous mutations in XPF also compromised XPF-Rpa1 and XPF-Slx4 interactions, and these cells are proficient in NER but deficient in ICLR and direct repeat recombination, establishing distinct interaction surfaces for NER vs. non-NER activities. Site-directed mutagenesis, UV and ICL sensitivity assays, co-immunoprecipitation, SSA and ICLR assays in yeast and human cells Nature communications High 29795289
2019 ERCC1/XPF is required for repair of DSBs containing DNA secondary structures, including AT-rich sequences from common fragile sites and G-quadruplexes (G4s); XPF inactivation is synthetically lethal with FANCM deficiency, and ERCC1/XPF-deficient cells are sensitized to G4-interacting compounds. siRNA knockdown and CRISPR knockout of XPF, DSB repair assays, synthetic lethality assay with FANCM, G4-interacting compound sensitivity assay iScience Medium 31153042
2019 SLX4IP binds simultaneously to SLX4 and XPF-ERCC1; disruption of one interaction also disrupts the other. SLX4IP binding to both proteins promotes the SLX4-XPF-ERCC1 interaction, especially after DNA damage, and maintains SLX4IP protein stability. SLX4IP depletion sensitizes cells to ICL-inducing agents and causes G2/M accumulation. Co-immunoprecipitation, domain interaction mapping, siRNA knockdown, ICL sensitivity assay, cell cycle analysis Nucleic acids research Medium 31495888
2019 TGFβ treatment leads to enhanced NER of bulky DNA damage via increased interaction between ERCC1-XPF and ERCC1-XPA and their nuclear localization; this effect requires intact TGFβ signaling (Smad4-dependent) and is abolished by ERCC1 knockdown. RNAi, co-immunoprecipitation of ERCC1-XPF and ERCC1-XPA, nuclear localization analysis, DNA damage repair assay (NER) Carcinogenesis Medium 30418489
2021 The ERCC1 R156W missense mutation disrupts a salt bridge below the XPA-binding pocket, causing dramatically reduced ERCC1 and XPF protein levels; mutant ERCC1 weakly interacts with NER and ICL repair proteins, shows diminished recruitment to DNA damage, and results in strongly reduced NER activity and increased chromosome breakage by crosslinkers. DSB repair was relatively normal in these patient-derived cells. Patient-derived fibroblasts and knock-in epithelial cells, protein interaction assays, NER activity assay, chromosome breakage assay, recruitment to DNA damage (immunofluorescence) The Journal of experimental medicine High 33315086
2021 XAB2 splicing factor interacts with ERCC1-XPF and XPG endonucleases outside of NER; the trimeric XAB2-ERCC1-XPF-XPG complex binds RNA:DNA hybrids under conditions favoring R-loop formation. XAB2 depletion leads to R-loop formation and DNA damage, and transcription-blocking DNA lesions trigger release of XAB2 from RNA targets. In vivo biotinylation tagging in mice, co-immunoprecipitation, RNA:DNA hybrid binding assay, siRNA knockdown, R-loop detection Nature communications High 34039990
2011 ERCC1 knockdown (but not XPF knockdown) causes multinucleation in human hepatocellular carcinoma cells (Huh7), HeLa, and human fibroblasts, with defects in metaphase and cytokinesis. This phenotype was rescued by ERCC1 overexpression and occurred in XPF-mutant fibroblasts after ERCC1 knockdown, but not after XPF knockdown. Other NER gene knockdowns (XPC, XPF) did not cause multinucleation, indicating an NER-independent, XPF-independent role for ERCC1 in mitotic progression. siRNA knockdown, ERCC1 overexpression rescue, live cell imaging, cell cycle analysis, phenotypic characterization in multiple cell lines DNA repair Medium 21839691
2024 SNRPA splicing factor controls alternative splicing of ERCC1 exon 8; SNRPA depletion causes ERCC1 exon 8 skipping, reduced ERCC1-XPF complex formation, and reversal of cisplatin resistance in lung adenocarcinoma cells. SNRPA overexpression has the opposite effect. m6A reader IGF2BP1 and RNA stabilizer ELAVL1 bind SNRPA mRNA and promote SNRPA-dependent ERCC1-E8(+) expression and cisplatin resistance. CRISPR/Cas9 knockout, shRNA knockdown, overexpression, RT-PCR for splicing, Western blot for ERCC1-XPF complex, cisplatin sensitivity assay, mouse xenograft model Advanced science Medium 39555714

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2007 DNA synthesis and repair genes RRM1 and ERCC1 in lung cancer. The New England journal of medicine 400 17314339
1986 Molecular characterization of the human excision repair gene ERCC-1: cDNA cloning and amino acid homology with the yeast DNA repair gene RAD10. Cell 334 2420469
2013 ERCC1 isoform expression and DNA repair in non-small-cell lung cancer. The New England journal of medicine 313 23514287
1992 ERCC1 and ERCC2 expression in malignant tissues from ovarian cancer patients. Journal of the National Cancer Institute 289 1433335
1994 Specific association between the human DNA repair proteins XPA and ERCC1. Proceedings of the National Academy of Sciences of the United States of America 278 8197174
2014 XPF-ERCC1 acts in Unhooking DNA interstrand crosslinks in cooperation with FANCD2 and FANCP/SLX4. Molecular cell 255 24726325
1994 Specific cleavage of model recombination and repair intermediates by the yeast Rad1-Rad10 DNA endonuclease. Science (New York, N.Y.) 247 8091230
2008 ERCC1-XPF endonuclease facilitates DNA double-strand break repair. Molecular and cellular biology 246 18541667
1998 DNA structural elements required for ERCC1-XPF endonuclease activity. The Journal of biological chemistry 191 9525876
1995 RAD1 and RAD10, but not other excision repair genes, are required for double-strand break-induced recombination in Saccharomyces cerevisiae. Molecular and cellular biology 190 7891718
2002 Yeast Tdp1 and Rad1-Rad10 function as redundant pathways for repairing Top1 replicative damage. Proceedings of the National Academy of Sciences of the United States of America 183 12368472
1993 Yeast DNA repair and recombination proteins Rad1 and Rad10 constitute a single-stranded-DNA endonuclease. Nature 183 8479526
1993 Co-correction of the ERCC1, ERCC4 and xeroderma pigmentosum group F DNA repair defects in vitro. The EMBO journal 160 8253090
2003 The mechanism of Mus81-Mms4 cleavage site selection distinguishes it from the homologous endonuclease Rad1-Rad10. Molecular and cellular biology 159 12724407
2011 Physiological consequences of defects in ERCC1-XPF DNA repair endonuclease. DNA repair 135 21612988
1990 RAD10, an excision repair gene of Saccharomyces cerevisiae, is involved in the RAD1 pathway of mitotic recombination. Molecular and cellular biology 135 2188090
2010 Multiple roles of the ERCC1-XPF endonuclease in DNA repair and resistance to anticancer drugs. Anticancer research 123 20944091
2009 XPF-ERCC1 participates in the Fanconi anemia pathway of cross-link repair. Molecular and cellular biology 119 19805513
2014 ATR pathway inhibition is synthetically lethal in cancer cells with ERCC1 deficiency. Cancer research 117 24662920
1996 Requirement of mismatch repair genes MSH2 and MSH3 in the RAD1-RAD10 pathway of mitotic recombination in Saccharomyces cerevisiae. Genetics 114 8849883
2015 The ERCC1 and ERCC4 (XPF) genes and gene products. Gene 112 26074087
1995 Purification and characterization of the XPF-ERCC1 complex of human DNA repair excision nuclease. The Journal of biological chemistry 112 7559382
2009 Significance of RRM1 and ERCC1 expression in resectable pancreatic adenocarcinoma. Oncogene 109 19543324
1995 Role of the Rad1 and Rad10 proteins in nucleotide excision repair and recombination. The Journal of biological chemistry 109 7559571
2002 Endogenous DNA abasic sites cause cell death in the absence of Apn1, Apn2 and Rad1/Rad10 in Saccharomyces cerevisiae. The EMBO journal 103 12032096
1993 Purification and characterization of the Saccharomyces cerevisiae RAD1/RAD10 endonuclease. The Journal of biological chemistry 102 8253764
2008 ERCC1/XPF limits L1 retrotransposition. DNA repair 84 18396111
2001 Activity of individual ERCC1 and XPF subunits in DNA nucleotide excision repair. Nucleic acids research 84 11160918
1996 Sequential binding of DNA repair proteins RPA and ERCC1 to XPA in vitro. Nucleic acids research 84 8972858
2009 Immunodetection of DNA repair endonuclease ERCC1-XPF in human tissue. Cancer research 83 19723666
2004 Physical and functional interaction between the XPF/ERCC1 endonuclease and hRad52. The Journal of biological chemistry 83 14734547
1992 Stable and specific association between the yeast recombination and DNA repair proteins RAD1 and RAD10 in vitro. Molecular and cellular biology 83 1620114
2010 The platinum-based treatments for advanced non-small cell lung cancer, is low/negative ERCC1 expression better than high/positive ERCC1 expression? A meta-analysis. Lung cancer (Amsterdam, Netherlands) 77 20541281
2008 Microarray-based genetic screen defines SAW1, a gene required for Rad1/Rad10-dependent processing of recombination intermediates. Molecular cell 77 18471978
1992 Specific complex formation between proteins encoded by the yeast DNA repair and recombination genes RAD1 and RAD10. Proceedings of the National Academy of Sciences of the United States of America 77 1518857
2018 Function and Interactions of ERCC1-XPF in DNA Damage Response. Molecules (Basel, Switzerland) 73 30563071
2013 Small molecule inhibitors of ERCC1-XPF protein-protein interaction synergize alkylating agents in cancer cells. Molecular pharmacology 69 23580445
2011 Excision repair cross-complementation group 1 (ERCC1) status and lung cancer outcomes: a meta-analysis of published studies and recommendations. PloS one 68 22022380
2013 ERCC1 and RRM1: ready for prime time? Journal of clinical oncology : official journal of the American Society of Clinical Oncology 67 23401439
2007 ERCC1 predicting chemoradiation resistance and poor outcome in oesophageal cancer. European journal of cancer (Oxford, England : 1990) 66 17976974
2005 ERCC1 and ERCC2 polymorphisms and adult glioma. Neuro-oncology 63 16212814
2011 ERCC5/XPG, ERCC1, and BRCA1 gene status and clinical benefit of trabectedin in patients with soft tissue sarcoma. Cancer 55 21287534
1993 Yeast DNA recombination and repair proteins Rad1 and Rad10 constitute a complex in vivo mediated by localized hydrophobic domains. Molecular microbiology 54 8361362
2004 Functional and physical interactions between ERCC1 and MSH2 complexes for resistance to cis-diamminedichloroplatinum(II) in mammalian cells. DNA repair 52 14706347
2014 USP45 deubiquitylase controls ERCC1-XPF endonuclease-mediated DNA damage responses. The EMBO journal 51 25538220
2013 Association between ERCC1 and XPA expression and polymorphisms and the response to cisplatin in testicular germ cell tumours. British journal of cancer 51 23807173
2010 Mec1/Tel1-dependent phosphorylation of Slx4 stimulates Rad1-Rad10-dependent cleavage of non-homologous DNA tails. DNA repair 48 20382573
2021 The splicing factor XAB2 interacts with ERCC1-XPF and XPG for R-loop processing. Nature communications 47 34039990
2010 ERCC1 and RRM1 in the international adjuvant lung trial by automated quantitative in situ analysis. The American journal of pathology 47 21224045
2004 Requirement of yeast Rad1-Rad10 nuclease for the removal of 3'-blocked termini from DNA strand breaks induced by reactive oxygen species. Genes & development 47 15371342
1985 Nucleotide sequence of the RAD10 gene of Saccharomyces cerevisiae. The EMBO journal 47 3912171
2012 Using protein microarray technology to screen anti-ERCC1 monoclonal antibodies for specificity and applications in pathology. BMC biotechnology 42 23171216
2012 The Rad1-Rad10 nuclease promotes chromosome translocations between dispersed repeats. Nature structural & molecular biology 41 22885325
2010 Multiple roles of ERCC1-XPF in mammalian interstrand crosslink repair. Environmental and molecular mutagenesis 41 20658648
1992 Renaturation of DNA catalysed by yeast DNA repair and recombination protein RAD10. Nature 40 1741062
1985 Molecular cloning and characterization of the yeast RAD10 gene and expression of RAD10 protein in E. coli. The EMBO journal 40 3896774
2001 ERCC1: a comparative genomic perspective. Environmental and molecular mutagenesis 38 11746756
2011 ERCC1 and XRCC1 as biomarkers for lung and head and neck cancer. Pharmacogenomics and personalized medicine 37 23226053
2003 The role of yeast DNA 3'-phosphatase Tpp1 and rad1/Rad10 endonuclease in processing spontaneous and induced base lesions. The Journal of biological chemistry 37 12783866
2019 ERCC1/XPF Is Important for Repair of DNA Double-Strand Breaks Containing Secondary Structures. iScience 35 31153042
2013 Role of Saw1 in Rad1/Rad10 complex assembly at recombination intermediates in budding yeast. The EMBO journal 35 23299942
2013 ERCC1 and ERCC2 variants predict survival in gastric cancer patients. PloS one 35 24023723
2012 Multiple DNA binding domains mediate the function of the ERCC1-XPF protein in nucleotide excision repair. The Journal of biological chemistry 33 22547097
2008 ERCC1 and ERCC2 polymorphisms and risk of idiopathic azoospermia in a Chinese population. Reproductive biomedicine online 33 18616887
2019 SLX4IP acts with SLX4 and XPF-ERCC1 to promote interstrand crosslink repair. Nucleic acids research 31 31495888
2017 ERCC1-XPF cooperates with CTCF and cohesin to facilitate the developmental silencing of imprinted genes. Nature cell biology 30 28368372
2014 Importance of EGFR/ERCC1 interaction following radiation-induced DNA damage. Clinical cancer research : an official journal of the American Association for Cancer Research 30 24780295
2011 The expression of ERCC1, RRM1, and BRCA1 in breast cancer according to the immunohistochemical phenotypes. Journal of Korean medical science 30 21394302
2008 Mutants defective in Rad1-Rad10-Slx4 exhibit a unique pattern of viability during mating-type switching in Saccharomyces cerevisiae. Genetics 29 18579504
2024 m6A-Modified SNRPA Controls Alternative Splicing of ERCC1 Exon 8 to Induce Cisplatin Resistance in Lung Adenocarcinoma. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 28 39555714
2021 ERCC1 mutations impede DNA damage repair and cause liver and kidney dysfunction in patients. The Journal of experimental medicine 25 33315086
2019 Targeting DNA Repair in Tumor Cells via Inhibition of ERCC1-XPF. Journal of medicinal chemistry 25 31369707
2015 Repair synthesis step involving ERCC1-XPF participates in DNA repair of the Top1-DNA damage complex. Carcinogenesis 25 26025908
2007 A neurological phenotype in mice with DNA repair gene Ercc1 deficiency. DNA repair 25 18221731
2005 The Rad1-Rad10 complex promotes the production of gross chromosomal rearrangements from spontaneous DNA damage in Saccharomyces cerevisiae. Genetics 25 15687264
2011 Identification of DNA repair gene Ercc1 as a novel target in melanoma. Pigment cell & melanoma research 24 21722328
1994 Purification of Rad1 protein from Saccharomyces cerevisiae and further characterization of the Rad1/Rad10 endonuclease complex. Biochemistry 24 8172904
1998 Alternative splicing of ERCC1 and cisplatin-DNA adduct repair in human tumor cell lines. International journal of molecular medicine 23 9852275
2020 XPF-ERCC1 protects liver, kidney and blood homeostasis outside the canonical excision repair pathways. PLoS genetics 22 32271760
2011 ERCC1 expression and outcomes in head and neck cancer treated with concurrent cisplatin and radiation. Anticancer research 21 22199271
2006 Involvement of ERCC1/XPF and XPG in oligodeoxynucleotide-directed gene modification. Oligonucleotides 21 16584298
2019 Expression of ERCC1 and TYMS in colorectal cancer patients and the predictive value of chemotherapy efficacy. Oncology letters 20 31423175
2019 TGF beta promotes repair of bulky DNA damage through increased ERCC1/XPF and ERCC1/XPA interaction. Carcinogenesis 19 30418489
2018 ERCC1-deficient cells and mice are hypersensitive to lipid peroxidation. Free radical biology & medicine 18 29860127
2017 Biological and predictive role of ERCC1 polymorphisms in cancer. Critical reviews in oncology/hematology 18 28259288
2017 Radiotherapy modulates expression of EGFR, ERCC1 and p53 in cervical cancer. Brazilian journal of medical and biological research = Revista brasileira de pesquisas medicas e biologicas 17 29160417
2013 ERCC1 and ERCC2 haplotype modulates induced BPDE-DNA adducts in primary cultured lymphocytes. PloS one 17 23593158
2011 The knock-down of ERCC1 but not of XPF causes multinucleation. DNA repair 17 21839691
2010 ERCC1 and XPF expression in human testicular germ cell tumors. Oncology reports 17 19956886
2008 XPF/ERCC4 and ERCC1: their products and biological roles. Advances in experimental medicine and biology 16 19181112
2025 Endothelial-Ercc1 DNA repair deficiency provokes blood-brain barrier dysfunction. Cell death & disease 15 39753531
2021 Enhancing the activity of platinum-based drugs by improved inhibitors of ERCC1-XPF-mediated DNA repair. Cancer chemotherapy and pharmacology 15 33399940
2020 The Ercc1-/Δ mouse model of accelerated senescence and aging for identification and testing of novel senotherapeutic interventions. Aging 15 33353886
2018 Distinct roles of XPF-ERCC1 and Rad1-Rad10-Saw1 in replication-coupled and uncoupled inter-strand crosslink repair. Nature communications 15 29795289
2012 Emodin affects ERCC1 expression in breast cancer cells. Journal of translational medicine 14 23046742
1990 Characterization of the RAD10 gene of Saccharomyces cerevisiae and purification of Rad10 protein. Biochemistry 14 2110825
2022 Rad1 and Rad10 Tied to Photolyase Regulators Protect Insecticidal Fungal Cells from Solar UV Damage by Photoreactivation. Journal of fungi (Basel, Switzerland) 13 36354891
2018 NDRG1 disruption alleviates cisplatin/sodium glycididazole-induced DNA damage response and apoptosis in ERCC1-defective lung cancer cells. The international journal of biochemistry & cell biology 13 29768183
2012 Accelerated loss of hearing and vision in the DNA-repair deficient Ercc1(δ/-) mouse. Mechanisms of ageing and development 13 22257940
2006 Single nucleotide polymorphisms and expression of ERCC1 and ERCC2 vis-à-vis chemotherapy drug cytotoxicity in human glioma. Journal of neuro-oncology 13 17151930

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