Affinage

ERCC1

DNA excision repair protein ERCC-1 · UniProt P07992

Length
297 aa
Mass
32.6 kDa
Annotated
2026-04-28
100 papers in source corpus 28 papers cited in narrative 28 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

ERCC1 is the non-catalytic subunit of the obligate ERCC1–XPF structure-specific endonuclease, which incises DNA on the 5′ side of duplex/single-strand junctions and is essential for nucleotide excision repair, interstrand crosslink (ICL) repair, single-strand annealing, and removal of 3′-blocked termini (PMID:9525876, PMID:7559382, PMID:17962301, PMID:15371342). ERCC1 stabilizes XPF protein, mediates recruitment to damage sites through direct interactions with XPA and RPA, and is itself regulated by USP45-dependent deubiquitylation that controls its translocation to DNA damage foci (PMID:20418188, PMID:8197174, PMID:25538220). In replication-coupled ICL repair, ERCC1–XPF performs unhooking incisions downstream of FANCD2 ubiquitylation and in cooperation with SLX4 and SNM1A, while RPA restores its endonuclease activity on nascent-strand-containing fork substrates (PMID:24726325, PMID:21896658, PMID:28607004). Beyond canonical DNA repair, ERCC1–XPF cooperates with CTCF–cohesin to maintain imprinted gene silencing and participates with XAB2 in processing R-loops (PMID:28368372, PMID:34039990).

Mechanistic history

Synthesis pass · year-by-year structured walk · 15 steps
  1. 1993 High

    Establishing that ERCC1 does not act alone but forms an obligate complex with XPF resolved the long-standing question of why mutations in three distinct complementation groups (ERCC1, ERCC4/XPF, XP-F) yielded overlapping repair defects.

    Evidence Co-purification and cross-complementation of repair defects in fractionated mammalian cell extracts

    PMID:8253090

    Open questions at the time
    • Stoichiometry and architecture of the complex unknown
    • Catalytic subunit not yet identified
  2. 1995 High

    Purification of the ERCC1–XPF heterodimer to homogeneity demonstrated intrinsic endonuclease activity preferring single-stranded and bubble-structured DNA, identifying the complex as the NER 5′ incision nuclease.

    Evidence Endonuclease assays with purified HeLa ERCC1–XPF on ssDNA, supercoiled, and bubble substrates

    PMID:7559382

    Open questions at the time
    • Minimal structural determinants for junction cleavage not defined
    • Which subunit provides catalytic activity unclear
  3. 1996 High

    Demonstrating that ERCC1 binds XPA on a surface distinct from the RPA-binding site, forming a ternary RPA–XPA–ERCC1 complex, established the recruitment mechanism bringing the 5′ endonuclease to the NER bubble.

    Evidence Surface plasmon resonance quantitative binding (KD measurements) and domain mapping of XPA

    PMID:8197174 PMID:8972858

    Open questions at the time
    • Whether ternary complex formation is regulated in vivo unknown
    • Structural basis of XPA–ERCC1 interface not resolved
  4. 1998 High

    Reconstitution with recombinant ERCC1–XPF on defined stem-loop, splayed-arm, and flap substrates established the structure-specific cleavage rules: incision occurs in duplex DNA 2–8 nt 5′ to a junction, requiring ≥4 unpaired nucleotides and divalent cations.

    Evidence Biochemical endonuclease assays with recombinant heterodimer on systematically varied synthetic substrates

    PMID:9525876

    Open questions at the time
    • Structural basis for junction recognition unresolved
    • How NER pre-incision complex positions the heterodimer in vivo unknown
  5. 1999 High

    Live-cell imaging revealed that ERCC1–XPF diffuses freely in the nucleus and is transiently immobilized at damage sites (~4 min per event), establishing that NER operates by sequential factor assembly rather than pre-assembled holocomplexes.

    Evidence GFP-ERCC1 FRAP in UV-irradiated CHO cells with dose-response kinetics

    PMID:10320375

    Open questions at the time
    • Order of arrival relative to other NER factors not determined
    • Whether dynamics differ between NER sub-pathways (GG-NER vs TC-NER) unknown
  6. 2001 High

    Reconstitution from separately expressed subunits showed that ERCC1's helix-hairpin-helix domain mediates heterodimerization with XPF and that XPF protein is unstable without ERCC1, explaining co-dependency observed in patient cells.

    Evidence Recombinant expression of individual subunits in E. coli; NER complementation; XPF immunoblotting

    PMID:11160918

    Open questions at the time
    • High-resolution structure of full-length heterodimer lacking
    • Post-translational modifications regulating stability unknown
  7. 2004 High

    Discovery that ERCC1–XPF interacts with hRad52 (stimulating nuclease activity while attenuating strand annealing) and with MSH2 (mediating NER-independent cisplatin resistance) expanded the functional repertoire of the complex beyond canonical NER.

    Evidence Co-immunoprecipitation, recombinant pulldown, and functional activity modulation assays; siRNA epistasis in XPA-deficient cells

    PMID:14706347 PMID:14734547

    Open questions at the time
    • In vivo significance of Rad52 interaction for SSA not directly tested
    • Structural basis of MSH2–ERCC1 interface unknown
  8. 2007 High

    Reporter-based assays in ERCC1-deficient cells demonstrated that ERCC1–XPF is required for both single-strand annealing and gene conversion, establishing its role in homology-directed DSB repair pathways beyond NER.

    Evidence Fluorescent SSA and gene conversion reporters in ERCC1-deficient mammalian cells with cell-cycle controls

    PMID:17962301

    Open questions at the time
    • Whether ERCC1–XPF trims 3′ flaps during gene conversion is assumed but not directly shown
    • Redundancy with other nucleases in SSA not fully defined
  9. 2008 High

    Demonstration that ERCC1–XPF participates in Ku86-independent end joining—with double-mutant mice showing additive chromosomal aberrations—revealed a distinct DSB repair function outside classical NHEJ.

    Evidence γ-irradiation sensitivity, γH2AX foci persistence, and in vitro DSB repair in Ercc1⁻/⁻ and Ercc1⁻/⁻Ku86⁻/⁻ mouse fibroblasts

    PMID:18541667

    Open questions at the time
    • Molecular mechanism of ERCC1–XPF recruitment to DSBs without Ku86 unclear
    • Whether this pathway corresponds to microhomology-mediated end joining not formally shown
  10. 2011 High

    Placing ERCC1–XPF and SNM1A in a sequential unhooking pathway for ICL repair—where ERCC1–XPF nicks and SNM1A digests past the crosslink—resolved how the two nucleases collaborate and explained why their individual loss triggers Mus81-dependent fork cleavage.

    Evidence In vitro reconstitution with purified SNM1A on ICL substrates; siRNA depletion and Mus81 epistasis in human cells

    PMID:21896658

    Open questions at the time
    • How ERCC1–XPF is positioned for the initial nick at stalled forks not clear
    • Whether additional nucleases contribute to unhooking in vivo not excluded
  11. 2014 High

    Xenopus extract reconstitution established the ordering of ICL repair: FANCD2 ubiquitylation recruits SLX4, which in turn positions XPF-ERCC1 for unhooking incisions, resolving the epistatic hierarchy within the Fanconi anemia pathway.

    Evidence Depletion/rescue in Xenopus egg extract replication-coupled ICL repair system

    PMID:19805513 PMID:24726325

    Open questions at the time
    • Whether SLX4 allosterically activates ERCC1–XPF catalysis is unknown
    • Structural basis of SLX4–XPF–ERCC1 ternary complex not resolved
  12. 2014 High

    Identification of USP45 as a deubiquitylase that directly removes ubiquitin from ERCC1 and controls its recruitment to damage foci revealed the first post-translational regulatory switch governing ERCC1 localization.

    Evidence In vitro deubiquitylation assay; USP45 KO cells with UV/ICL sensitivity and impaired ERCC1 foci formation

    PMID:25538220

    Open questions at the time
    • Identity of the E3 ligase that ubiquitylates ERCC1 unknown
    • Which ubiquitin site(s) on ERCC1 are modified not mapped
    • Whether USP45 regulation is cell-cycle dependent not tested
  13. 2017 High

    Showing that RPA selectively restores ERCC1–XPF activity on ICL-containing replication fork structures bearing a nascent leading strand explained how the endonuclease overcomes the inhibitory effect of the nascent strand during fork-coupled repair.

    Evidence In vitro endonuclease assay with purified ERCC1–XPF and RPA on defined ICL-fork substrates

    PMID:28607004

    Open questions at the time
    • Whether RPA acts by remodeling the substrate or allosterically activating the enzyme is unresolved
    • Contribution of other fork-binding proteins in vivo not assessed
  14. 2017 High

    The unexpected finding that ERCC1–XPF interacts with CTCF–cohesin at imprinting control regions and that Ercc1 loss disrupts imprinted gene silencing without altering DNA methylation revealed a chromatin-maintenance function outside canonical DNA repair.

    Evidence In vivo biotinylation pulldown, ChIP, and expression analysis in Ercc1-deficient mouse livers

    PMID:28368372

    Open questions at the time
    • Whether ERCC1–XPF nuclease activity is required for this function unknown
    • Whether this extends to other CTCF-regulated loci not tested
    • Mechanism by which DNA damage triggers CTCF relocalization unclear
  15. 2021 High

    Discovery that XAB2 bridges ERCC1–XPF and XPG to form a trimeric complex that binds R-loops linked the NER endonucleases to co-transcriptional genome maintenance and RNA processing.

    Evidence In vivo biotinylation tagging in mice; RNA:DNA hybrid binding assays; XAB2 depletion phenotype with R-loop accumulation

    PMID:34039990

    Open questions at the time
    • Whether ERCC1–XPF cleaves R-loops directly or facilitates their resolution indirectly is unresolved
    • Relationship to TC-NER not delineated

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include the identity of the E3 ubiquitin ligase targeting ERCC1, high-resolution structures of ERCC1–XPF engaged with NER and ICL repair intermediates, and whether the nuclease activity is required for its chromatin-organizing and R-loop processing functions.
  • Full-length ERCC1–XPF structure on physiological DNA substrates unavailable
  • E3 ligase for ERCC1 ubiquitylation not identified
  • Nuclease-dead separation-of-function mutants not tested in chromatin/R-loop contexts

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140097 catalytic activity, acting on DNA 4 GO:0140096 catalytic activity, acting on a protein 3 GO:0003677 DNA binding 2
Localization
GO:0005634 nucleus 2 GO:0005694 chromosome 1
Pathway
R-HSA-73894 DNA Repair 8 R-HSA-1643685 Disease 4 R-HSA-8953854 Metabolism of RNA 1
Partners
MSH2RAD52RPASLX4USP45XAB2XPAXPF
Complex memberships
ERCC1–XPF heterodimerSLX4–XPF–ERCC1 complexXAB2–ERCC1-XPF–XPG complex

Evidence

Reading pass · 28 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1994 ERCC1 protein specifically interacts with XPA (human DNA repair factor) both in vivo (two-hybrid system) and in vitro (recombinant proteins), with initial domain mapping showing that defined regions of ERCC1 and XPA mediate this interaction; XPA may play a role in loading the ERCC1-containing incision complex onto damaged DNA sites. Yeast two-hybrid assay and in vitro pulldown with recombinant proteins; domain mapping Proceedings of the National Academy of Sciences of the United States of America High 8197174
1993 ERCC1 is part of a functional protein complex (~100 kDa native) with XPF (ERCC4), as shown by co-correction of repair defects in rodent group 1, group 4, and XP-F cell extracts; the ERCC1 polypeptide co-purifies with the XPF-correcting activity and is reduced in all three complementation groups. In vitro NER reconstitution assay with fractionated cell extracts; immunoblotting; co-correction of XP-F, ERCC4, and ERCC1 defects The EMBO journal High 8253090
1995 XPF (ERCC4) and ERCC1 form a heterodimeric complex purified from HeLa cells; the complex has endonuclease activity preferring single-stranded DNA and bubble-structured duplex DNA, and its nicking of UV-damaged supercoiled DNA is stimulated by human RPA; complementation of ERCC-1, ERCC-4, and XP-F repair defects was demonstrated biochemically. Protein purification from HeLa cells; endonuclease assays on ssDNA, supercoiled DNA, and bubble substrates; complementation of cell-free extracts The Journal of biological chemistry High 7559382
1998 Recombinant ERCC1-XPF heterodimer, purified from insect cells, is a structure-specific endonuclease that cleaves at duplex/single-strand junctions intrinsically (without RPA or other proteins); it requires divalent cations, a minimum of 4–8 unpaired nucleotides, and incises the duplex strand 2–8 nt from the junction on the 5' side; one single-stranded arm (3' or 5') is necessary and sufficient for positioning of cleavage. Biochemical endonuclease assay with recombinant protein on defined stem-loop, splayed-arm, and flap substrates; divalent cation titration; substrate structure-activity analysis The Journal of biological chemistry High 9525876
1999 In living cells, GFP-tagged ERCC1/XPF diffuses freely throughout the nucleus in the absence of DNA damage (diffusion coefficient ~15 µm²/s); UV-induced DNA damage causes transient, dose-dependent immobilization of the complex (~4 min per repair event), indicating NER operates by assembly of individual factors at damage sites rather than pre-assembled holocomplexes, and ERCC1/XPF acts distributively. Live-cell fluorescence microscopy of GFP-ERCC1/XPF in CHO cells; fluorescence recovery after photobleaching (FRAP); UV dose-response experiments Science (New York, N.Y.) High 10320375
1996 RPA and ERCC1 bind to distinct, non-overlapping regions of XPA, and a ternary RPA–XPA–ERCC1 complex can form in vitro; surface plasmon resonance measurements yield KD values of 1.9×10⁻⁸ M (RPA–XPA) and 2.5×10⁻⁷ M (ERCC1–XPA); binding of RPA and ERCC1 to XPA is sequential. In vitro binding assays; surface plasmon resonance (Biacore); domain mapping of XPA binding regions Nucleic acids research High 8972858
2001 Separately produced recombinant ERCC1 and XPF subunits can reconstitute functional ERCC1-XPF heterodimer; XPF is unstable in mammalian cells without ERCC1 partner; the helix-hairpin-helix domain of ERCC1 and the nuclease domain of XPF are required for endonuclease activity; sequence comparison revealed ancient duplication linking the C-terminal regions of ERCC1 and XPF families (basis for heterodimerization). Recombinant expression of individual subunits in E. coli; NER complementation assay in cell extracts; immunoassays for XPF stability Nucleic acids research High 11160918
2004 XPF/ERCC1 forms a stable complex with hRad52 in human cell-free extracts via direct protein–protein interaction through the N-terminal domain of hRad52 and the XPF subunit; complex formation stimulates ERCC1-XPF endonuclease activity and simultaneously attenuates hRad52 strand-annealing activity. Co-immunoprecipitation from human cell extracts; recombinant protein pulldown; endonuclease and strand-annealing activity assays The Journal of biological chemistry High 14734547
2004 ERCC1 physically interacts with the MSH2 mismatch repair complex in HeLa cell extracts; the minimal ERCC1 region required for MSH2 co-immunoprecipitation maps to the C-terminal domain (residues 184–260), overlapping the XPF-binding domain; ERCC1 and MSH2 co-operate in resistance to cisplatin ICL damage independently of NER (shown by ERCC1 RNAi sensitization of XPA-deficient cells to cisplatin but not UV, and loss of this effect in MSH2/XPA double-deficient cells). Co-immunoprecipitation from HeLa extracts; tagged ERCC1 domain mapping in COS7 cells; siRNA knockdown; cell survival assays DNA repair High 14706347
2008 ERCC1-XPF endonuclease is required for DSB repair in mammals via a Ku86-independent end-joining mechanism; ERCC1/XPF-deficient fibroblasts are hypersensitive to γ-irradiation with persistent γH2AX foci; Ercc1⁻/⁻Ku86⁻/⁻ double-mutant fibroblasts show greater chromosomal aberrations; in vitro DSB repair of 3' overhang substrates produces large deletions in the absence of ERCC1-XPF. γ-irradiation sensitivity assays; γH2AX foci persistence; in vitro DSB repair assay; double-mutant mouse and cell analysis (Ercc1⁻/⁻ Ku86⁻/⁻) Molecular and cellular biology High 18541667
2009 XPF-ERCC1 complex participates in the Fanconi anemia ICL repair pathway; unhooking of ICL by XPF-ERCC1 is required for stable chromatin localization of monoubiquitinated FANCD2 and subsequent HR-mediated DSB repair; FANCD2 monoubiquitination itself occurs but persists longer and chromatin-bound FANCD2 foci are dramatically reduced in XPF-ERCC1-deficient cells after crosslinking agent treatment. Analysis of FANCD2 ubiquitination and foci in Ercc1⁻/⁻ mouse cells, XPF-deficient human and hamster cells; chromatin fractionation; immunofluorescence Molecular and cellular biology High 19805513
2011 Human SNM1A (5'→3' exonuclease) and XPF-ERCC1 collaborate to initiate ICL repair in replicating cells; purified SNM1A can load from a nick and digest past an ICL; hSNM1A-depleted and ERCC1-depleted cells both accumulate replication-associated DSBs that are Mus81-induced, indicating failure of the SNM1A/XPF-ERCC1 unhooking pathway triggers Mus81-mediated fork cleavage. Biochemical assay with purified SNM1A on ICL substrates; siRNA depletion of hSNM1A or ERCC1; γH2AX and Mus81 epistasis in human cells Genes & development High 21896658
2014 XPF-ERCC1 performs the unhooking incisions during replication-coupled ICL repair in cooperation with SLX4/FANCP; efficient recruitment of XPF-ERCC1 and SLX4 to the ICL depends on FANCD2 and its ubiquitylation, establishing the order of events in the FA/ICL repair pathway. Xenopus egg extract ICL repair assay; depletion/rescue experiments; analysis of XPF-ERCC1 and SLX4 recruitment Molecular cell High 24726325
2014 USP45 deubiquitylase associates with ERCC1 via a short acidic motif outside the USP45 catalytic domain; USP45 deubiquitylates ERCC1 in vitro (wild-type but not ERCC1-binding-deficient mutant); USP45 knockout cells accumulate ubiquitylated ERCC1, are hypersensitive to UV and ICL agents, and show impaired ERCC1 translocation to DNA damage-induced subnuclear foci. Co-immunoprecipitation; in vitro deubiquitylation assay; USP45 knockout cells; UV and crosslinker sensitivity; immunofluorescence of ERCC1 foci The EMBO journal High 25538220
2017 RPA selectively restores XPF-ERCC1 endonuclease activity on ICL-containing model replication fork structures bearing a nascent leading strand (which otherwise inhibits cleavage); XPF-ERCC1 incises the ICL fork in the presence of RPA, and SNM1A can then load from the nick and digest past the crosslink to complete unhooking. In vitro endonuclease assay with purified XPF-ERCC1 and RPA on defined ICL-containing replication fork substrates; SNM1A exonuclease assay The EMBO journal High 28607004
2012 Multiple C-terminal DNA-binding domains of ERCC1-XPF contribute to NER activity; mutations in the helix-hairpin-helix domain of ERCC1 and the nuclease domain of XPF abolish cleavage on model substrates; mutations in multiple DNA-binding domains are needed to significantly diminish NER in vitro and in vivo, suggesting protein–protein contacts in the NER complex compensate for weakened DNA binding; ICL repair requires tighter substrate binding than NER. Mutagenesis of DNA-binding domains; in vitro cleavage assays; NER complementation in cell extracts and in vivo; mitomycin C vs. UV sensitivity comparison The Journal of biological chemistry High 22547097
2013 The ERCC1-202 isoform is the sole functionally active isoform in NER and ICL repair; only isoform 202 interacts with RPA, XPA, and XPF, and XPF protein stability requires expression of isoform 202; the other three isoforms cannot rescue abnormal mitosis (FA-like phenotype) in ERCC1-deficient NSCLC cells. Expression of individual ERCC1 isoforms in ERCC1-deficient cells; co-immunoprecipitation of XPA, RPA, XPF; NER and ICL repair assays; mitosis phenotype rescue Cell cycle (Georgetown, Tex.) High 24036546
2017 ERCC1-XPF complex interacts in vivo with the insulator binding protein CTCF, cohesin subunits SMC1A and SMC3, and MBD2; the complex co-localizes with ATRX at promoters and imprinting control regions (ICRs) of imprinted genes during postnatal hepatic development; loss of Ercc1 or MMC-induced DNA damage triggers CTCF relocalization to heterochromatin, dissociation of the CTCF-cohesin complex and ATRX from promoters/ICRs, altered histone marks, and aberrant developmental expression of imprinted genes without altering DNA methylation. In vivo biotinylation tagging and pulldown in mice; ChIP; immunoprecipitation; gene expression analysis in Ercc1-deficient mouse livers Nature cell biology High 28368372
2021 Splicing factor XAB2 interacts with ERCC1-XPF and XPG endonucleases outside canonical NER; the trimeric XAB2–ERCC1-XPF–XPG complex binds RNA:DNA hybrids (R-loops); XAB2 depletion causes aberrant intron retention, R-loop accumulation, and DNA damage; transcription-blocking lesions trigger release of XAB2 from RNA targets. In vivo biotinylation tagging in mice; immunoprecipitation; RNA binding assays; XAB2 depletion phenotype analysis; R-loop detection Nature communications High 34039990
2010 ERCC1 knockdown reduces XPF protein levels (but not mRNA), indicating ERCC1 is required for XPF protein stability; downregulation of either XPF, ERCC1, or both diminishes repair of cisplatin intrastrand crosslinks and ICLs, and ICL-induced DSBs persist in the absence of XPF-ERCC1. RNAi knockdown of XPF, ERCC1, or both; ELISA-based crosslink repair assay; alkaline comet assay; γH2AX foci; Western blot for protein stability DNA repair High 20418188
2007 ERCC1-XPF endonuclease is required for single-strand annealing (SSA) and gene conversion (synthesis-dependent strand annealing) in mammalian somatic cells, as demonstrated by reduced frequencies of both pathways in ERCC1-deficient cells; SSA is not frequent in G1-arrested cells. Fluorescent reporter-based SSA and gene conversion assay in ERCC1-deficient mammalian cells; cell cycle arrest experiments; CDK2/ATM/Chk1/DNA-PK inhibitors Nucleic acids research High 17962301
2004 Genetic evidence (Rad1-Rad10 yeast ortholog of ERCC1-XPF) demonstrates that Rad1-Rad10 nuclease is required for the removal of 3'-blocked termini (including 3'-phosphoglycolate ends) from DNA strand breaks induced by reactive oxygen species (H₂O₂); Rad1-Rad10 acts in parallel with Apn1 and Apn2 for this function; in vitro, Rad1-Rad10 cleaves DNA with a 3'-phosphoglycolate terminus. Genetic epistasis in yeast (apn1Δ apn2Δ rad1Δ/rad10Δ mutants); in vitro cleavage assay with 3'-phosphoglycolate-modified substrate; camptothecin/H₂O₂ sensitivity Genes & development High 15371342
2019 ERCC1/XPF is required for efficient repair of DSBs containing DNA secondary structures, including AT-rich sequences from common fragile sites and G-quadruplexes (G4s); removal of non-homologous sequences at DSBs by ERCC1/XPF is a rate-limiting step for homologous recombination; synthetic lethality exists between XPF and DNA translocase FANCM. XPF loss-of-function in mammalian cells; HR reporter assays; G4-stabilizing compound sensitivity; FANCM-XPF double-deficiency epistasis iScience Medium 31153042
2019 SLX4IP binds simultaneously to SLX4 and XPF-ERCC1; disruption of either interaction also disrupts the other; SLX4IP binding promotes the SLX4–XPF-ERCC1 interaction, especially after DNA damage; SLX4IP depletion sensitizes cells to ICL agents and causes G2/M accumulation. Co-immunoprecipitation; depletion by siRNA; ICL sensitivity assays; cell cycle analysis Nucleic acids research Medium 31495888
2014 EGFR interacts with ERCC1 following ionizing radiation-induced DNA damage (validated by mass spectrometry interactome, biochemical co-IP, and proximity ligation assay); ERCC1-dependent DNA repair contributes to IR-induced strand-break repair independently of DNA-PKcs, as shown by combined EGFR and ERCC1 knockdown experiments with comet and γH2AX assays. EGFR interactome by mass spectrometry; co-IP validation; proximity ligation assay; siRNA double knockdown; comet assay; γH2AX foci; cell survival Clinical cancer research : an official journal of the American Association for Cancer Research Medium 24780295
2015 ERCC1-XPF and RPA participate in repair synthesis of Top1-attached nick DNA lesions (mimicking CPT-induced Top1-DNA complexes); purified ERCC1-XPF shows nuclease activity on 3'-phosphotyrosyl bond nick-containing DNA in the presence of RPA; ERCC1-XPF and RPA co-localize in CPT-treated cells; repair synthesis of Tyr-nick DNA requires NER factors including ERCC1-XPF, RPA, Polδ, FEN1, and ligase 1. In vitro endonuclease assay with purified ERCC1-XPF/RPA on Tyr-nick DNA; in vitro repair synthesis reconstitution; co-localization in CPT-treated cells Carcinogenesis Medium 26025908
2006 MZF1 functions as a transcriptional repressor of ERCC1; MZF1 binds to an MZF1-like site in the ERCC1 promoter (EMSA); overexpression of MZF1 represses ERCC1 promoter activity; MZF1 mRNA decreases upon cisplatin exposure, coinciding with increased ERCC1 transcription; AP1 and MZF1 binding sites in the drug-responsive ERCC1 promoter region regulate cisplatin-induced ERCC1 upregulation. CAT reporter assay; EMSA; co-transfection/promoter activity assay; quantitative PCR Biochemical pharmacology Medium 16426580
2024 SNRPA (spliceosome component, m6A-modified via IGF2BP1/ELAVL1) controls alternative splicing of ERCC1 exon 8; SNRPA depletion causes ERCC1 exon 8 skipping, reduces ERCC1-XPF complex formation, and reverses cisplatin resistance in lung adenocarcinoma cells; siRNAs targeting ERCC1 isoforms containing exon 8 reversed SNRPA-enhanced cisplatin resistance. CRISPR/Cas9 and shRNA knockdown; splice isoform analysis; co-immunoprecipitation for ERCC1-XPF complex; cisplatin sensitivity; mouse xenograft model Advanced science (Weinheim, Baden-Wurttemberg, Germany) Medium 39555714

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1994 Messenger RNA levels of XPAC and ERCC1 in ovarian cancer tissue correlate with response to platinum-based chemotherapy. The Journal of clinical investigation 380 8040325
1999 Action of DNA repair endonuclease ERCC1/XPF in living cells. Science (New York, N.Y.) 291 10320375
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 254 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 245 18541667
2005 ERCC1 expression is a predictor of survival in resected patients with non-small cell lung cancer. Chest 234 15764785
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 182 12368472
1993 Co-correction of the ERCC1, ERCC4 and xeroderma pigmentosum group F DNA repair defects in vitro. The EMBO journal 160 8253090
2010 Downregulation of XPF-ERCC1 enhances cisplatin efficacy in cancer cells. DNA repair 144 20418188
2007 Current status of excision repair cross complementing-group 1 (ERCC1) in cancer. Cancer treatment reviews 137 17707593
1990 RAD10, an excision repair gene of Saccharomyces cerevisiae, is involved in the RAD1 pathway of mitotic recombination. Molecular and cellular biology 135 2188090
2011 Physiological consequences of defects in ERCC1-XPF DNA repair endonuclease. DNA repair 134 21612988
2007 The ERCC1/XPF endonuclease is required for efficient single-strand annealing and gene conversion in mammalian cells. Nucleic acids research 134 17962301
2010 Multiple roles of the ERCC1-XPF endonuclease in DNA repair and resistance to anticancer drugs. Anticancer research 123 20944091
2011 Human SNM1A and XPF-ERCC1 collaborate to initiate DNA interstrand cross-link repair. Genes & development 122 21896658
2009 XPF-ERCC1 participates in the Fanconi anemia pathway of cross-link repair. Molecular and cellular biology 118 19805513
2014 ATR pathway inhibition is synthetically lethal in cancer cells with ERCC1 deficiency. Cancer research 116 24662920
2005 Reduced hematopoietic reserves in DNA interstrand crosslink repair-deficient Ercc1-/- mice. The EMBO journal 114 15692571
1996 Requirement of mismatch repair genes MSH2 and MSH3 in the RAD1-RAD10 pathway of mitotic recombination in Saccharomyces cerevisiae. Genetics 114 8849883
1995 Purification and characterization of the XPF-ERCC1 complex of human DNA repair excision nuclease. The Journal of biological chemistry 112 7559382
2015 The ERCC1 and ERCC4 (XPF) genes and gene products. Gene 111 26074087
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
1993 Purification and characterization of the Saccharomyces cerevisiae RAD1/RAD10 endonuclease. The Journal of biological chemistry 102 8253764
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
2004 Physical and functional interaction between the XPF/ERCC1 endonuclease and hRad52. The Journal of biological chemistry 83 14734547
2009 Immunodetection of DNA repair endonuclease ERCC1-XPF in human tissue. Cancer research 82 19723666
2018 Functional Polymorphisms at ERCC1/XPF Genes Confer Neuroblastoma Risk in Chinese Children. EBioMedicine 80 29544698
2008 Microarray-based genetic screen defines SAW1, a gene required for Rad1/Rad10-dependent processing of recombination intermediates. Molecular cell 77 18471978
2009 The DNA repair proteins BRCA1 and ERCC1 as predictive markers in sporadic ovarian cancer. International journal of cancer 76 19035454
2018 A meiotic XPF-ERCC1-like complex recognizes joint molecule recombination intermediates to promote crossover formation. Genes & development 75 29440262
2018 Function and Interactions of ERCC1-XPF in DNA Damage Response. Molecules (Basel, Switzerland) 72 30563071
2007 ERCC1 as a risk stratifier in platinum-based chemotherapy for nonsmall-cell lung cancer. Current opinion in pulmonary medicine 71 17534174
2013 Small molecule inhibitors of ERCC1-XPF protein-protein interaction synergize alkylating agents in cancer cells. Molecular pharmacology 68 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
2008 Polymorphisms of the NER pathway genes, ERCC1 and XPD are associated with esophageal adenocarcinoma risk. Cancer causes & control : CCC 68 18478337
2007 ERCC1 predicting chemoradiation resistance and poor outcome in oesophageal cancer. European journal of cancer (Oxford, England : 1990) 66 17976974
2015 Inhibition of the ERCC1-XPF structure-specific endonuclease to overcome cancer chemoresistance. DNA repair 63 25956741
2005 ERCC1 and ERCC2 polymorphisms and adult glioma. Neuro-oncology 63 16212814
2007 Prediction of response to chemotherapy by ERCC1 immunohistochemistry and ERCC1 polymorphism in ovarian cancer. International journal of gynecological cancer : official journal of the International Gynecological Cancer Society 59 17961161
2009 ERCC1 and XRCC1 gene polymorphisms predict response to neoadjuvant radiochemotherapy in esophageal cancer. Journal of gastrointestinal surgery : official journal of the Society for Surgery of the Alimentary Tract 56 19421825
2003 Clear cell tumors have higher mRNA levels of ERCC1 and XPB than other histological types of epithelial ovarian cancer. Clinical cancer research : an official journal of the American Association for Cancer Research 56 14614013
2011 Molecular Characteristics of ERCC1-Negative versus ERCC1-Positive Tumors in Resected NSCLC. Clinical cancer research : an official journal of the American Association for Cancer Research 55 21750204
2017 RPA activates the XPF-ERCC1 endonuclease to initiate processing of DNA interstrand crosslinks. The EMBO journal 53 28607004
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 50 25538220
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
2010 Mec1/Tel1-dependent phosphorylation of Slx4 stimulates Rad1-Rad10-dependent cleavage of non-homologous DNA tails. DNA repair 46 20382573
2021 The splicing factor XAB2 interacts with ERCC1-XPF and XPG for R-loop processing. Nature communications 44 34039990
2013 ERCC1 function in nuclear excision and interstrand crosslink repair pathways is mediated exclusively by the ERCC1-202 isoform. Cell cycle (Georgetown, Tex.) 43 24036546
2012 Using protein microarray technology to screen anti-ERCC1 monoclonal antibodies for specificity and applications in pathology. BMC biotechnology 42 23171216
2011 Correlations among ERCC1, XPB, UBE2I, EGF, TAL2 and ILF3 revealed by gene signatures of histological subtypes of patients with epithelial ovarian cancer. Oncology reports 42 21971700
2011 RT-PCR versus immunohistochemistry for correlation and quantification of ERCC1, BRCA1, TUBB3 and RRM1 in NSCLC. Lung cancer (Amsterdam, Netherlands) 42 21996087
2010 Multiple roles of ERCC1-XPF in mammalian interstrand crosslink repair. Environmental and molecular mutagenesis 41 20658648
2014 Melatonin attenuates cisplatin-induced HepG2 cell death via the regulation of mTOR and ERCC1 expressions. World journal of hepatology 40 24799992
2012 The Rad1-Rad10 nuclease promotes chromosome translocations between dispersed repeats. Nature structural & molecular biology 40 22885325
2003 Characterization of premature liver polyploidy in DNA repair (Ercc1)-deficient mice. Hepatology (Baltimore, Md.) 38 14512883
2013 Thymidylate synthase and ERCC1 as predictive markers in patients with pulmonary adenocarcinoma treated with pemetrexed and cisplatin. Lung cancer (Amsterdam, Netherlands) 37 23523421
2019 ERCC1-XPF deficiency is a predictor of olaparib induced synthetic lethality and platinum sensitivity in epithelial ovarian cancers. Gynecologic oncology 35 30797591
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 34 23299942
2011 XRCC1 and ERCC1 variants modify malignant mesothelioma risk: a case-control study. Mutation research 33 21277872
2008 ERCC1 and ERCC2 polymorphisms and risk of idiopathic azoospermia in a Chinese population. Reproductive biomedicine online 33 18616887
2006 MZF1 possesses a repressively regulatory function in ERCC1 expression. Biochemical pharmacology 33 16426580
2012 Multiple DNA binding domains mediate the function of the ERCC1-XPF protein in nucleotide excision repair. The Journal of biological chemistry 32 22547097
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
2013 ERCC1 and XRCC1 expression predicts survival in bladder cancer patients receiving combined trimodality therapy. Molecular and clinical oncology 30 24649183
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
1996 Identification of functional domains within the RAD1.RAD10 repair and recombination endonuclease of Saccharomyces cerevisiae. The Journal of biological chemistry 28 8702799
2015 The predictive value of ERCC1 and p53 for the effect of panobinostat and cisplatin combination treatment in NSCLC. Oncotarget 27 25944617
2015 Catechols and 3-hydroxypyridones as inhibitors of the DNA repair complex ERCC1-XPF. Bioorganic & medicinal chemistry letters 27 26318993
2012 Is there a role for the quantification of RRM1 and ERCC1 expression in pancreatic ductal adenocarcinoma? BMC cancer 26 22436573
2010 Evaluation of ERCC1 expression for cisplatin sensitivity in human hepatocellular carcinoma. Annals of surgical oncology 26 21076943
2024 m6A-Modified SNRPA Controls Alternative Splicing of ERCC1 Exon 8 to Induce Cisplatin Resistance in Lung Adenocarcinoma. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 25 39555714
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
2006 Effects of ERCC1 expression in peripheral blood on the risk of head and neck cancer. European journal of cancer prevention : the official journal of the European Cancer Prevention Organisation (ECP) 25 16679872
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
1996 Roles of XPG and XPF/ERCC1 endonucleases in UV-induced immunostaining of PCNA in fibroblasts. Experimental cell research 24 8660947
1994 Purification of Rad1 protein from Saccharomyces cerevisiae and further characterization of the Rad1/Rad10 endonuclease complex. Biochemistry 24 8172904
2018 Rs3212986 polymorphism, a possible biomarker to predict smoking-related lung cancer, alters DNA repair capacity via regulating ERCC1 expression. Cancer medicine 23 30453383
2007 No association of ERCC1 C8092A and T19007C polymorphisms to cancer risk: a meta-analysis. European journal of human genetics : EJHG 23 17522621
1995 Genomic copy number changes of DNA repair genes ERCC1 and ERCC2 in human gliomas. Journal of neuro-oncology 23 8583241
2015 DNA repair gene ERCC1 C118T polymorphism predicts sensitivity of recurrent esophageal cancer to radiochemotherapy in a Chinese population. Thoracic cancer 22 26557912
1985 Molecular cloning of the RAD10 gene of Saccharomyces cerevisiae. Gene 22 3891515
2014 Combination of TRAP1 and ERCC1 Expression Predicts Clinical Outcomes in Metastatic Colorectal Cancer Treated with Oxaliplatin/5-Fluorouracil. Cancer research and treatment 21 24520224
2014 ERCC1 siRNA ameliorates drug resistance to cisplatin in gastric carcinoma cell lines. Molecular medicine reports 21 24699918
2006 Involvement of ERCC1/XPF and XPG in oligodeoxynucleotide-directed gene modification. Oligonucleotides 21 16584298
2020 XPF-ERCC1 protects liver, kidney and blood homeostasis outside the canonical excision repair pathways. PLoS genetics 20 32271760