Affinage

ERCC6L

DNA excision repair protein ERCC-6-like · UniProt Q2NKX8

Length
1250 aa
Mass
141.1 kDa
Annotated
2026-06-09
53 papers in source corpus 29 papers cited in narrative 31 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 8/8 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

ERCC6L (PICH) is an SNF2-family ATP-dependent DNA translocase that operates at centromeres, kinetochores, and ultrafine anaphase DNA bridges (UFBs) to ensure faithful sister-chromatid disjunction during mitosis (PMID:17218258, PMID:26643143). It binds duplex DNA with an affinity that increases under tension mimicking the mitotic spindle pulling on a UFB, and uses ATP hydrolysis to translocate along and extend DNA (PMID:23973328). Its recruitment and activity are tightly regulated: Cdk1 phosphorylates PICH at T1063 to dock Plk1 and direct PICH to inner centromeres and inter-kinetochore threads (PMID:17218258), while SUMO2/3 modification by PIASy lowers its DNA-binding capacity (PMID:25564610) and three SUMO-interacting motifs govern its centromeric versus chromatin-bridge functions (PMID:27230136). Functionally, PICH directly stimulates topoisomerase IIα catalytic activity (PMID:26643143) and partners with TOP3α to extrude DNA loops that generate dense positive supercoiling, promoting decatenation (PMID:30936532); in parallel it acts as a tension-dependent nucleosome remodeler that unwraps and slides histones to keep UFBs histone-free, cooperating with BLM and RIF1 in bridge resolution (PMID:21743438, PMID:36433994, PMID:39704103). Its translocase activity also disperses SUMO2/3-modified chromosomal proteins, attenuating SUMOylated TopoIIα and modulating spindle-checkpoint signaling via Bub1 abundance (PMID:32877270, PMID:39919802). Outside mitosis, PICH promotes extensive replication fork reversal downstream of the ZATT–TOP2A–SUMO axis (PMID:33296677). Loss of PICH produces chromatin bridges, micronuclei, p53 activation, and chromosomal rearrangements (PMID:39704103), and in mice causes defective fetal hematopoiesis through cytoplasmic dsDNA accumulation and cGAS-STING-driven type I interferon (PMID:35037428). ERCC6L is recurrently co-opted in cancer, where it participates in transcriptional complexes driving cyclin A1 and cell-cycle progression (PMID:37646571, PMID:37667329).

Mechanistic history

Synthesis pass · year-by-year structured walk · 18 steps
  1. 2007 High

    Established PICH as a Plk1 partner whose mitotic localization is set by Cdk1 phosphorylation, defining how a DNA-acting enzyme is targeted to centromeres at the right cell-cycle moment.

    Evidence Co-IP, phosphosite mapping of T1063, siRNA and immunofluorescence in human cells

    PMID:17218258

    Open questions at the time
    • Did not define the enzymatic DNA substrate
    • Mechanism of centromere selectivity beyond Plk1 docking unresolved
  2. 2007 High

    Showed PICH-coated inter-kinetochore threads are tension-dependent, DNase-sensitive catenated/stretched chromatin linked to topoisomerase II and cohesin, framing PICH as a marker and effector of unresolved sister-chromatid links.

    Evidence Immunofluorescence with DNase, cohesin depletion, ICRF-193 in human cells

    PMID:17218258 PMID:17956945

    Open questions at the time
    • Did not establish direct biochemical action on the threads
    • Causality between PICH and thread resolution untested at this stage
  3. 2009 High

    Corrected the original claim of a PICH role in the spindle assembly checkpoint, attributing the apparent SAC defect to off-target siRNA suppression of Mad2 and refining PICH's function to chromosome mechanics rather than checkpoint signaling.

    Evidence siRNA specificity analysis with BAC complementation and multiple oligos

    PMID:19904549

    Open questions at the time
    • Left open whether PICH influences SAC indirectly, later revisited
  4. 2011 High

    Defined PICH as a nucleosome remodeler that recruits BLM to anaphase threads, linking PICH activity to histone-free bridge resolution and prevention of centromeric micronuclei.

    Evidence PICH-BLM Co-IP, RNAi, in vitro nucleosome remodeling with purified PICH

    PMID:21743438

    Open questions at the time
    • Did not resolve order of remodeling versus decatenation
    • BLM helicase contribution to PICH-driven resolution not separated
  5. 2012 Medium

    Dissected PICH ATPase requirements, showing the ATPase domain prevents chromatin bridges and controls localization while being dispensable for UFB resolution, separating its functions mechanistically.

    Evidence Antibody microinjection and ATPase-mutant siRNA rescue with quantitative bridge/UFB scoring

    PMID:22527115 PMID:22563370

    Open questions at the time
    • Distinct molecular outputs of ATPase activity at bridges vs UFBs unclear
    • Single-lab phenotypic readouts
  6. 2013 High

    Reconstituted PICH biophysics, revealing tension-enhanced DNA binding, ATP-dependent translocation, DNA extension, and reduced force-induced melting—explaining how PICH preferentially acts on stretched UFB DNA.

    Evidence Optical tweezers, single-molecule fluorescence, microfluidics with purified PICH

    PMID:23973328

    Open questions at the time
    • Did not connect translocation directly to decatenation in vivo
    • Substrate handoff to topoisomerases not addressed here
  7. 2015 High

    Demonstrated PICH directly stimulates topoisomerase II and that its ATPase activity is needed for timely UFB and rDNA resolution, providing the catalytic link between PICH and decatenation.

    Evidence PICH knockout in DT40 and human cells, ICRF-193 sensitivity, in vitro topo II activity assay

    PMID:26643143

    Open questions at the time
    • Structural basis of PICH-topo II stimulation undefined
    • Whether stimulation occurs at all genomic loci unknown
  8. 2015 High

    Identified PICH as a SUMO2/3 substrate (via PIASy) and SUMO-binder of PARP1 and TopoIIα, with SUMOylation reducing DNA binding, establishing SUMO as a regulatory layer on PICH activity.

    Evidence Xenopus extracts, in vitro SUMOylation of recombinant PICH, Co-IP, DNA binding assay

    PMID:25564610

    Open questions at the time
    • In vivo consequences of PICH SUMOylation not fully mapped
    • Functional SUMO sites on PICH not enumerated
  9. 2016 Medium

    Mapped three SUMO-interacting motifs to distinct functions—SIM3 for centromeric localization and others for bridge prevention—showing SUMO recognition partitions PICH's mitotic roles.

    Evidence Conditional expression of SIM-deficient PICH mutants with localization readouts

    PMID:27230136

    Open questions at the time
    • SUMO partners read by each SIM not individually identified
    • UFB localization remained SIM-independent and unexplained
  10. 2017 High

    Solved the crystal structure of a novel PICH TPR domain–BEND3 BEN domain interface, providing the first structural account of a PICH protein interaction in mitosis.

    Evidence Co-IP, in vitro interaction, 2.2 Å crystal structure with structure-guided mutagenesis

    PMID:28977671

    Open questions at the time
    • Functional role of BEND3 in PICH-dependent processes not established
    • How TPR-BEN binding affects translocase activity unknown
  11. 2019 High

    Reconstituted a PICH-TOP3α machine generating reverse-gyrase-like positive supercoiling through PICH loop extrusion and TOP3α relaxation, defining a topological mechanism for sister-chromatid disjunction.

    Evidence In vitro reconstitution with purified PICH and TOP3α, magnetic tweezers

    PMID:30936532

    Open questions at the time
    • In vivo demonstration of supercoiling at UFBs absent
    • Coordination with TopoIIα decatenation not integrated
  12. 2020 High

    Placed PICH in replication stress responses, showing TOP2A-SUMO-dependent recruitment to stalled forks where it acts downstream of HLTF/ZRANB3/SMARCAL1 to enable extensive fork reversal, extending PICH function beyond mitosis.

    Evidence Knockdown epistasis, EM fork reversal assay, PLA, Co-IP

    PMID:33296677

    Open questions at the time
    • Direct topological substrate at forks not visualized
    • Relationship to mitotic UFB function not reconciled
  13. 2020 High

    Showed PICH translocase disperses SUMO2/3 foci and attenuates SUMOylated TopoIIα, linking PICH's enzymatic activity to clearance of SUMO-modified chromosomal proteins.

    Evidence AID-based PICH depletion, translocase-mutant rescue, in vitro SUMO-TopoIIα assay, IF

    PMID:32877270

    Open questions at the time
    • Full repertoire of SUMO substrates remodeled by PICH incomplete
    • Mechanism of SUMO-protein removal by translocation unclear
  14. 2022 High

    Visualized PICH as a tension- and ATP-dependent nucleosome remodeler that unwraps and slides histones, mechanistically explaining how UFBs become histone-free under spindle tension.

    Evidence Dual-trap optical tweezers with fluorescence imaging on nucleosome arrays

    PMID:36433994

    Open questions at the time
    • Fate of displaced histones in vivo unknown
    • Integration with TopoIIα/TOP3α decatenation not shown
  15. 2022 High

    Linked PICH loss to organismal phenotype, showing Pich-KO causes cytoplasmic dsDNA, cGAS-STING activation, and interferon-driven loss of fetal hematopoietic stem cells, rescued by cGAS or Ifnar1 deletion.

    Evidence Pich-KO mouse, HSC transplantation, cGAS/Ifnar1 double-KO rescue, dsDNA and IFN assays

    PMID:35037428

    Open questions at the time
    • Source of cytoplasmic dsDNA (unresolved bridges vs micronuclei) not pinned
    • Tissue specificity of the requirement unexplained
  16. 2023 Medium

    Defined synthetic-lethal and compensatory genetic relationships (FIRRM/FIGNL1 and RAD52) that create dependency on PICH for genome stability, identifying potential therapeutic vulnerabilities.

    Evidence Genome-wide CRISPR screens, Co-IP, UFB and RAD51/RAD52 foci, fork dynamics assays

    PMID:37347663 PMID:39561207

    Open questions at the time
    • Direct mechanistic interaction between PICH and these pathways unresolved
    • Single-lab screen validations
  17. 2023 Medium

    Implicated ERCC6L in oncogenic cell-cycle and transcriptional programs, forming a complex with RNA Pol II and ATF4 at CCNA1 and interacting with KIF4A to drive proliferation.

    Evidence Co-IP, ChIP, ATPase-mutant, organoid/PDX and conditional-KO mouse studies

    PMID:37646571 PMID:37667329

    Open questions at the time
    • Whether transcriptional roles are separable from translocase function unclear
    • Direct DNA-binding at promoters versus indirect recruitment not resolved
  18. 2025 High

    Resolved a dual role for PICH translocase in UFB resolution—generating single-stranded UFBs and stimulating TopoIIα—and tied PICH loss to DNA damage, micronuclei, p53 activation, and chromosomal rearrangements; also reconnected PICH to SAC via SUMO-protein remodeling and Bub1 control.

    Evidence Domain-mutant rescue (PICHK128A, BLM/RIF1-recruitment mutant), WGS, ssUFB IF, topo IIα assay, proteomics, Mad1/Bub1 IF

    PMID:39704103 PMID:39919802

    Open questions at the time
    • Precise molecular event producing ssUFBs undefined
    • How SUMO-protein remodeling sets Bub1 levels mechanistically unclear

Open questions

Synthesis pass · forward-looking unresolved questions
  • How PICH's distinct biochemical activities—loop-extruding supercoiling with TOP3α, TopoIIα stimulation, nucleosome remodeling, and SUMO-protein dispersal—are spatially and temporally coordinated into a single coherent bridge-resolution program remains unresolved.
  • No unified in vivo model linking the in vitro activities
  • Order and hand-off between TopoIIα, TOP3α, BLM, and RIF1 at a single UFB undefined

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140657 ATP-dependent activity 4 GO:0003677 DNA binding 3 GO:0098772 molecular function regulator activity 3 GO:0140097 catalytic activity, acting on DNA 2 GO:0140110 transcription regulator activity 2
Localization
GO:0005694 chromosome 3 GO:0005634 nucleus 1
Pathway
R-HSA-1640170 Cell Cycle 4 R-HSA-73894 DNA Repair 3 R-HSA-4839726 Chromatin organization 2 R-HSA-69306 DNA Replication 2
Partners
ATF4BEND3BLMKIF4APLK1RIF1TOP2ATOP3A

Evidence

Reading pass · 31 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2007 PICH is an interaction partner and substrate of Plk1; Cdk1 phosphorylates PICH on T1063, which recruits Plk1 to PICH and controls its localization to kinetochores, inner centromeres, and inter-kinetochore threads during mitosis. Co-immunoprecipitation, phosphorylation mapping, siRNA knockdown, immunofluorescence Cell High 17218258
2007 PICH-positive inter-kinetochore threads are tension-dependent, DNase-sensitive, and exacerbated by premature cohesin loss or topoisomerase II inhibition, suggesting they represent stretched centromeric chromatin/catenated DNA. Immunofluorescence, DNase treatment, siRNA knockdown of cohesins, topoisomerase II inhibitor (ICRF-193) treatment Cell High 17218258
2007 Depletion of PICH causes selective loss of Mad2 from kinetochores and abrogates the spindle checkpoint; however, subsequent work showed this effect was due to off-target siRNA suppression of Mad2, not a direct PICH function in the SAC. siRNA knockdown, immunofluorescence for Mad2, rescue with Mad2-expressing BAC, multiple siRNA oligonucleotides Cell / Chromosoma High 17218258 19904549
2009 PICH does not have a direct role in spindle assembly checkpoint (SAC) signaling; siRNAs targeting PICH that abolished the SAC also reduced Mad2 mRNA/protein as an off-target effect. siRNAs that effectively deplete PICH without affecting Mad2 do not abolish SAC functionality. siRNA specificity analysis, BAC complementation expressing murine Mad2, Plk1 depletion/inhibition rescue experiments Chromosoma High 19904549
2007 Depletion of topoisomerase IIα leads to abnormal persistence of PICH-coated anaphase threads connecting segregating chromatids and shortening of the metaphase inter-kinetochore distance, indicating functional cooperation between PICH and topo IIα at centromeres. Conditional-lethal topo IIα mutant cell line, immunofluorescence for PICH, FISH Journal of cell science Medium 17956945
2008 PICH recruits Plk1 to chromosome arms during mitosis; disruption of the PICH-Plk1 interaction abolishes Plk1 localization on chromosome arms. Both PICH phosphorylation and its ATPase activity are required for mitotic chromosome compaction. Co-immunoprecipitation, dominant-negative PICH mutants (Plk1-binding deficient, ATP-binding deficient), immunofluorescence Cell cycle Medium 18418076
2010 PICH and Plk1 coordinately maintain prometaphase chromosome arm architecture; PICH knockdown causes loss of Plk1 from chromosome arms and produces disorganized 'wavy' chromosomes with an open/X-shaped configuration that is prevented by topoisomerase II inhibitor ICRF-193, indicating the PICH-Plk1 complex maintains chromosome architecture in a topo II-dependent manner. siRNA knockdown, immunofluorescence for Plk1/condensin/cohesin, ICRF-193 treatment Molecular biology of the cell Medium 20130082
2011 PICH directly binds BLM and enables BLM localization to anaphase centromeric threads. Purified recombinant PICH has nucleosome remodeling activity in vitro. PICH- or BLM-depleted cells fail to resolve anaphase threads, which then contain histones and centromere markers, forming centromeric micronuclei. Co-immunoprecipitation (PICH-BLM), RNAi knockdown, in vitro nucleosome remodeling assay with purified recombinant PICH, immunofluorescence The EMBO journal High 21743438
2012 ATPase activity of PICH is critical for its function: an intact ATPase domain is required to prevent chromatin bridge formation but is not required for UFB resolution. ATPase activity is also required for temporal and spatial control of PICH localization to chromatin. Antibody microinjection, siRNA rescue with ATPase-mutant PICH, quantitative analysis of UFB and chromatin bridge frequencies Chromosoma Medium 22527115
2012 BLM and PICH cooperate to recruit active topoisomerase IIα to centromeres; both BLM-deficient and PICH-deficient prometaphase cells display centromere structural changes, higher centromeric non-disjunction in cohesin-free conditions, and defective topoisomerase IIα centromere recruitment. RNAi knockdown, immunofluorescence, chromatin immunoprecipitation, electron microscopy, FISH PloS one Medium 22563370
2013 PICH binds duplex DNA with remarkably high affinity, and this affinity increases with tension-induced DNA stretching, mimicking the mitotic spindle on a UFB. PICH performs ATP-dependent protein translocation and extends DNA. PICH binding diminishes force-induced DNA melting. Microfluidics, single-molecule fluorescence microscopy, optical tweezers, in vitro assays with purified PICH Molecular cell High 23973328
2015 PICH directly stimulates the catalytic activity of topoisomerase II in vitro. Deletion of PICH causes chromosome structural abnormalities, hypersensitivity to topo II inhibitor ICRF-193, sister chromatid non-disjunction in anaphase, and cytokinesis failure. The timely resolution of UFBs and rDNA structures depends on the ATPase activity of PICH. PICH knockout in avian (DT40) cells and human cell line, ICRF-193 sensitivity assay, in vitro topo II activity assay with purified PICH protein Nature communications High 26643143
2015 PICH is modified by SUMO2/3 on mitotic chromosomes and in vitro, mediated by the SUMO E3 ligase PIASy. PICH interacts with SUMOylated PARP1 and SUMOylated topoisomerase IIα. SUMOylation of PICH significantly reduces its DNA binding capability, suggesting SUMO regulates PICH ATPase activity. Xenopus egg extract assays, co-immunoprecipitation with SUMOylated substrates, in vitro SUMOylation assay with purified recombinant human PICH, DNA binding assay The Journal of biological chemistry High 25564610
2016 PICH contains three SUMO-interacting motifs (SIMs). SIM3 (near the C-terminus) is critical for PICH centromeric localization, while the other two SIMs function in chromatin bridge prevention. All SIMs are dispensable for PICH localization to ultrafine anaphase DNA bridges. Conditional PICH expression, SIM-deficient PICH mutants, immunofluorescence Cell cycle Medium 27230136
2017 PICH interacts with the BEN domain-containing protein BEND3 in human cells during mitosis via a novel TPR domain (in PICH) – BEN domain (in BEND3) interface. The crystal structure of the TPR-BEN complex was determined at 2.2 Å resolution, and structure-guided mutagenesis identified residues critical for the interaction. Co-immunoprecipitation in human cells, purification of full-length proteins, in vitro biochemical interaction assay, crystal structure at 2.2 Å (MAD phasing), structure-guided mutagenesis Nucleic acids research High 28977671
2019 PICH and Topoisomerase 3α (TOP3A) together create an extraordinarily high density of positive DNA supercoiling, analogous to a reverse-gyrase activity, driven by PICH progressively extruding hypernegatively supercoiled DNA loops that are relaxed by TOP3A. In vitro reconstitution with purified human PICH and TOP3α, magnetic tweezers single-molecule assay Nature structural & molecular biology High 30936532
2020 Upon replication stress, PICH is recruited to stalled replication forks in a manner dependent on TOP2A SUMOylation by ZATT. PICH acts downstream of HLTF/ZRANB3/SMARCAL1 (which initiate limited fork reversal) to promote extensive fork reversal by resolving topological barriers. Disruption of the ZATT-TOP2A-PICH axis results in accumulation of partially reversed forks and enhanced genome instability. siRNA/shRNA knockdown of pathway components, replication fork reversal assay (electron microscopy), proximity ligation assay, co-immunoprecipitation Molecular cell High 33296677
2020 PICH specifically disperses SUMO2/3 foci on mitotic chromosomes; this requires its DNA translocase activity. PICH uses its SUMO-binding ability to attenuate SUMOylated TopoIIα activity in vitro. Conditional depletion of PICH causes retention of SUMO2/3-modified chromosomal proteins including TopoIIα. Auxin-inducible degron (AID) PICH depletion, translocase-deficient PICH mutant rescue, in vitro TopoIIα activity assay with SUMOylated substrate, immunofluorescence Molecular biology of the cell High 32877270
2022 PICH is a tension- and ATP-dependent nucleosome remodeler: under tension mimicking anaphase chromatin bridges, PICH facilitates nucleosome unwrapping and subsequently slides remaining histones along the DNA. Single-molecule assay: dual-trap optical tweezers combined with fluorescence imaging of PICH and histones on nucleosome-array constructs in vitro Nature communications High 36433994
2022 PICH deficiency in mice leads to defective embryonic hematopoiesis: Pich-KO fetal liver HSCs show elevated cytoplasmic dsDNA and activation of the cGAS-STING pathway, resulting in excessive type I interferon production and apoptosis. Deletion of Ifnar1 or cGAS reverses the defective hematopoiesis. Pich knockout mouse model, HSC transplantation assay, cGAS/Ifnar1 double knockout rescue, cytoplasmic dsDNA staining, interferon quantification Advanced science High 35037428
2023 PICH forms a transcriptional complex with RNA polymerase II and ATF4 at the CCNA1 (cyclin A1) promoter in an ATPase-dependent manner, promoting cyclin A1 transcription and accelerating S-phase progression, thereby impairing 5-FU chemosensitivity in gastric cancer. Co-immunoprecipitation (PICH-PolII-ATF4), ChIP at CCNA1 promoter, ATPase-deficient PICH mutant, organoid and patient-derived xenograft assays Cancer research Medium 37646571
2023 FIRRM (C1orf112) and FIGNL1 inactivation creates synthetic lethality with PICH (ERCC6L). FIRRM interacts with and stabilizes FIGNL1; loss of either leads to UFB formation, prolonged RAD51 foci, and impaired replication fork dynamics, creating dependency on PICH for viability. Genome-wide CRISPR knockout screen, co-immunoprecipitation (FIRRM-FIGNL1), UFB imaging, RAD51 foci quantification, replication fork dynamics assay Cell reports Medium 37347663
2023 ERCC6L directly interacts with KIF4A; both proteins cooperate in mitosis and breast cancer cell progression. ERCC6L accelerates the cell cycle by regulating the G2/M checkpoint via p53/p21/CDK1/Cyclin B and PLK/CDC25C/CDK1/Cyclin B signaling pathways. Co-immunoprecipitation (ERCC6L-KIF4A), ERCC6L conditional knockout mouse model, western blotting of pathway components, cell cycle analysis Journal of experimental & clinical cancer research Medium 37667329
2024 RAD52 deficiency increases ERCC6L-coated anaphase UFBs, and ERCC6L depletion causes elevated RAD52 foci in prometaphase and interphase cells. RAD52 and ERCC6L have a compensatory/synthetic-lethal relationship for genome stability in mitosis, enhanced by replication stress and topo IIα inhibition. Genome-wide CRISPR knockout screen, RAD52-deficient cell lines, ERCC6L depletion, UFB quantification, 53BP1 foci quantification, hydroxyurea and ICRF-193 treatment PLoS genetics Medium 39561207
2025 PICH's translocase activity plays a dual role in UFB resolution: facilitating generation of single-stranded UFBs and stimulating topoisomerase IIα. A PICH mutant impairing UFB recruitment of BLM and RIF1 partially inhibits UFB resolution, while a translocase-inactive mutant (PICHK128A) completely fails to resolve UFBs and also inhibits single-stranded UFB formation and induces hypocondensed chromosomes. PICH depletion in diploid cells induces DNA damage, micronuclei, p53 activation, G1-phase delay, and chromosomal rearrangements (translocations and inversions) detected by whole-genome sequencing. PICH depletion, domain mutant rescue (translocase-inactive PICHK128A, BLM/RIF1 recruitment mutant), whole-genome sequencing, single-stranded UFB immunofluorescence, topo IIα stimulation assay Nucleic acids research High 39704103
2025 PICH impacts spindle assembly checkpoint (SAC) activity via both its DNA translocase activity and SUMO-interaction (SIM) activities. Defects in either PICH remodeling or SIM function delay mitotic progression by activating the SAC (extended Mad1 foci at centromeres). PICH controls Bub1 kinetochore abundance, and loss of PICH leads to increased Bub1 at kinetochores, implicating PICH in SAC regulation through SUMOylated chromosomal protein remodeling. Conditional PICH depletion/replacement cell lines, translocase-deficient and SIM-deficient PICH mutants, proteomics of SUMOylated chromosomal proteins, immunofluorescence for Mad1 and Bub1 Life science alliance Medium 39919802
2022 PICH regulates the expression of Nrf2 (antioxidant transcription factor) and is present on Nrf2 and antioxidant gene promoters as shown by ChIP. PICH expression is upregulated during oxidative stress and forms a regulatory loop with Nrf2. PICH depletion reduces Nrf2 expression and impairs antioxidant response, increasing ROS. ChIP on Nrf2 and antioxidant gene promoters, PICH overexpression rescue in PICH-depleted cells, ROS measurement, western blotting Epigenomes Low 36278682
2026 ERCC6L stabilizes HIF-1α by inhibiting its hydroxylation and ubiquitin-mediated degradation, thereby upregulating aerobic glycolysis (Warburg effect) in lung adenocarcinoma cells. The ERCC6L/HIF-1α axis promotes cancer stemness. Overexpression/knockdown of ERCC6L, HIF-1α hydroxylation and ubiquitination assays, western blotting, in vitro and in vivo functional assays Cell death & disease Low 40691138
2026 ERCC6L transcriptionally activates PLK1 by directly binding to its PLK1 promoter. This ERCC6L-PLK1 axis drives aerobic glycolysis, upregulating GLUT1, LDHA, PKM2, and HK2 in melanoma cells. ChIP-qPCR, dual-luciferase reporter assay, western blotting, metabolic flux analysis Life sciences Low 41564924
2026 ERCC6L activates the E3 ubiquitin ligase PJA2, which mediates K48-linked polyubiquitination and proteasomal degradation of p53, attenuating its tumor-suppressive function in lung adenocarcinoma. ERCC6L knockout suppresses tumor growth and metastasis via the PJA2/p53 axis in vivo. Co-immunoprecipitation, ubiquitination assays (K48-linked), ERCC6L knockout mouse xenograft, western blotting Respiratory research Low 42063149
2026 PICH cooperates with the telomere-associated protein RIF1 to maintain genomic stability during iPSC reprogramming under replication stress, and overexpression of Pich improves iPSC reprogramming efficiency by alleviating replication stress. Pich knockout and overexpression in iPSC reprogramming system, RIF1 co-depletion epistasis, genomic stability assays The FEBS journal Low 41981724

Source papers

Stage 0 corpus · 53 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2007 PICH, a centromere-associated SNF2 family ATPase, is regulated by Plk1 and required for the spindle checkpoint. Cell 287 17218258
2015 PICH promotes sister chromatid disjunction and co-operates with topoisomerase II in mitosis. Nature communications 98 26643143
2013 PICH: a DNA translocase specially adapted for processing anaphase bridge DNA. Molecular cell 88 23973328
2011 PICH and BLM limit histone association with anaphase centromeric DNA threads and promote their resolution. The EMBO journal 79 21743438
2020 The ZATT-TOP2A-PICH Axis Drives Extensive Replication Fork Reversal to Promote Genome Stability. Molecular cell 67 33296677
2007 Depletion of topoisomerase IIalpha leads to shortening of the metaphase interkinetochore distance and abnormal persistence of PICH-coated anaphase threads. Journal of cell science 67 17956945
2009 Re-examination of siRNA specificity questions role of PICH and Tao1 in the spindle checkpoint and identifies Mad2 as a sensitive target for small RNAs. Chromosoma 57 19904549
2001 Stabilization of local structures by pi-CH and aromatic-backbone amide interactions involving prolyl and aromatic residues. Protein engineering 51 11579222
2012 Bloom's syndrome and PICH helicases cooperate with topoisomerase IIα in centromere disjunction before anaphase. PloS one 50 22563370
2019 PICH and TOP3A cooperate to induce positive DNA supercoiling. Nature structural & molecular biology 37 30936532
2010 PICH and cotargeted Plk1 coordinately maintain prometaphase chromosome arm architecture. Molecular biology of the cell 37 20130082
2017 ERCC6L, a DNA helicase, is involved in cell proliferation and associated with survival and progress in breast and kidney cancers. Oncotarget 35 28178669
2012 On the regulation, function, and localization of the DNA-dependent ATPase PICH. Chromosoma 35 22527115
2008 Targeting Plk1 to chromosome arms and regulating chromosome compaction by the PICH ATPase. Cell cycle (Georgetown, Tex.) 31 18418076
2018 Loss of PICH Results in Chromosomal Instability, p53 Activation, and Embryonic Lethality. Cell reports 30 30232008
2016 PICH promotes mitotic chromosome segregation: Identification of a novel role in rDNA disjunction. Cell cycle (Georgetown, Tex.) 30 27565185
2019 Loss of PICH promotes chromosome instability and cell death in triple-negative breast cancer. Cell death & disease 29 31160555
2015 SUMOylation regulates polo-like kinase 1-interacting checkpoint helicase (PICH) during mitosis. The Journal of biological chemistry 25 25564610
2023 FIRRM/C1orf112 is synthetic lethal with PICH and mediates RAD51 dynamics. Cell reports 24 37347663
2018 ERCC6L that is up-regulated in high grade of renal cell carcinoma enhances cell viability in vitro and promotes tumor growth in vivo potentially through modulating MAPK signalling pathway. Cancer gene therapy 24 30459398
2019 ERCC6L promotes cell growth and invasion in human colorectal cancer. Oncology letters 21 31289493
2020 ERCC6L promotes the progression of hepatocellular carcinoma through activating PI3K/AKT and NF-κB signaling pathway. BMC cancer 20 32891122
2016 SUMO-interacting motifs (SIMs) in Polo-like kinase 1-interacting checkpoint helicase (PICH) ensure proper chromosome segregation during mitosis. Cell cycle (Georgetown, Tex.) 20 27230136
2018 shRNA knockdown of DNA helicase ERCC6L expression inhibits human breast cancer growth. Molecular medicine reports 17 30066865
2005 Ercc6l, a gene of SNF2 family, may play a role in the teratogenic action of alcohol. Toxicology letters 17 15917148
2022 PICH Supports Embryonic Hematopoiesis by Suppressing a cGAS-STING-Mediated Interferon Response. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 16 35037428
2023 ERCC6L facilitates the onset of mammary neoplasia and promotes the high malignance of breast cancer by accelerating the cell cycle. Journal of experimental & clinical cancer research : CR 15 37667329
2023 PICH Activates Cyclin A1 Transcription to Drive S-Phase Progression and Chemoresistance in Gastric Cancer. Cancer research 14 37646571
2022 PICH acts as a force-dependent nucleosome remodeler. Nature communications 14 36433994
2017 A novel TPR-BEN domain interaction mediates PICH-BEND3 association. Nucleic acids research 14 28977671
2020 PICH regulates the abundance and localization of SUMOylated proteins on mitotic chromosomes. Molecular biology of the cell 13 32877270
2020 Upregulation of Excision Repair Cross-Complementation Group 6-Like (ERCC6L) Promotes Tumor Growth in Hepatocellular Carcinoma. Digestive diseases and sciences 11 32347436
2022 A pan-cancer analysis of the oncogenic role of ERCC6L. BMC cancer 9 36550435
2021 ERCC6L promotes cell growth and metastasis in gastric cancer through activating NF-κB signaling. Aging 9 34425559
2022 ERCC6L is a biomarker and therapeutic target for non-small cell lung adenocarcinoma. Medical oncology (Northwood, London, England) 8 35150321
2021 Regulation of mitotic chromosome architecture and resolution of ultrafine anaphase bridges by PICH. Cell cycle (Georgetown, Tex.) 8 34530686
2023 ERCC6L facilitates the progression of laryngeal squamous cell carcinoma by the binding of FOXM1 and KIF4A. Cell death discovery 5 36726012
2023 Pan-genomic comparison of a potential solvent-tolerant alkaline protease-producing Exiguobacterium sp. TBG-PICH-001 isolated from a marine habitat. 3 Biotech 5 37854939
2016 Isolation and Proteomics Analysis of Barley Centromeric Chromatin Using PICh. Journal of proteome research 5 27142171
2016 Characterization of the NTPR and BD1 interacting domains of the human PICH-BEND3 complex. Acta crystallographica. Section F, Structural biology communications 5 27487930
2024 PICH deficiency limits the progression of MYC-induced B-cell lymphoma. Blood cancer journal 4 38253636
2007 Polo delivers a PICH to the kinetochore. Cell 4 17218250
2025 ERCC6L-mediated stabilization of HIF-1α enhances glycolysis and stemness properties of lung adenocarcinoma cells. Cell death & disease 3 40691138
2024 Anti-Proliferation Effect of Nodosin on Hepatocellular Carcinoma Cells Via The ERCC6L/PI3K/AKT/Axis. Journal of biochemical and molecular toxicology 2 39503234
2025 The interplay of the translocase activity and protein recruitment function of PICH in ultrafine anaphase bridge resolution and genomic stability. Nucleic acids research 1 39704103
2024 PICH, A protein that maintains genomic stability, can promote tumor growth. Gene 1 39491600
2024 RAD52 and ERCC6L/PICH have a compensatory relationship for genome stability in mitosis. PLoS genetics 1 39561207
2026 ERCC6L promotes cutaneous melanoma progression via PLK1-mediated aerobic glycolysis: Mechanisms and therapeutic implications. Life sciences 0 41564924
2026 PICH facilitates iPSC reprogramming by alleviating genomic instability induced by DNA replication stress. The FEBS journal 0 41981724
2026 ERCC6L drives lung adenocarcinoma metastasis: a PJA2/p53 ubiquitination-dependent mechanism. Respiratory research 0 42063149
2025 PICH impacts the spindle assembly checkpoint via its DNA translocase and SUMO-interaction activities. Life science alliance 0 39919802
2023 RAD52 and ERCC6L/PICH have a compensatory relationship for genome stability in mitosis. bioRxiv : the preprint server for biology 0 37662271
2022 PLK-1 Interacting Checkpoint Helicase, PICH, Mediates Cellular Oxidative Stress Response. Epigenomes 0 36278682

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