Affinage

RECQL

ATP-dependent DNA helicase Q1 · UniProt P46063

Length
649 aa
Mass
73.5 kDa
Annotated
2026-06-10
88 papers in source corpus 37 papers cited in narrative 38 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

RECQL encodes an ATP-dependent, 3′→5′ DNA helicase of the RecQ family that operates as a central guardian of replication fork integrity and genome stability (PMID:7961977, PMID:12419808). Its catalytic core couples ATP hydrolysis to strand separation through a winged-helix β-hairpin (Y564 at its tip) and a zinc-binding RQC motif, both of which are required for unwinding while being dispensable for the enzyme's distinct strand-annealing mode (PMID:19151156, PMID:21059676, PMID:27248010); an α-helix at the zinc-binding/WH-domain interface acts as a conformational switch toggling between unwinding and annealing activities (PMID:34751402). Beyond classical duplex unwinding, RECQL catalyzes strand annealing, unidirectional 3′→5′ Holliday-junction branch migration, D-loop disruption, and G-quadruplex resolution (PMID:15899892, PMID:16260474, PMID:18495662, PMID:40966504), with its oligomeric state biasing it toward unwinding (monomers/dimers) versus annealing and junction resolution (higher-order oligomers) (PMID:17227144, PMID:34496242). Functionally, RECQL is loaded at replication origins at S-phase onset to support origin firing and normal fork progression, protects stalled forks from MRE11-dependent breakage, and drives restart of TOP1-inhibitor-induced reversed forks—an activity restrained by PARP1 poly(ADP-ribosyl)ation in a regulatory axis further modulated by nucleoplasmic Lamin A/C and H3K9me3 (PMID:20065033, PMID:32820027, PMID:23396353). RECQL controls cellular RPA availability for replication, and RPA reciprocally stimulates its processivity and protein-displacement activity (PMID:15096578, PMID:26455304, PMID:24895130). It physically interacts with RPA, RAD51, the mismatch-repair factors MSH2/6 and EXO1, FEN-1, Ku70/80, TRF2, and PARP1, embedding it in homologous recombination, mismatch repair, NHEJ, telomere maintenance, and checkpoint signaling (PMID:15096578, PMID:15886194, PMID:18074021, PMID:23650516, PMID:24623817, PMID:25774876, PMID:22542292); loss of RECQL causes aneuploidy, elevated sister-chromatid exchanges, chromosomal breakage, defective ATR/Chk1 checkpoint activation, and sensitivity to ionizing radiation and topoisomerase poisons (PMID:17158923, PMID:31444271). RECQL also functions in transcriptional regulation, cooperating with FOXA1 to open chromatin at ESR1 regulatory regions in a helicase-dependent manner (PMID:33468559). A biallelic p.A459S mutation in the zinc-binding domain causes RECON syndrome, a progeroid genome-instability disorder, by selectively compromising ATPase, helicase, and fork-restoration activity while sparing strand annealing (PMID:35025765).

Mechanistic history

Synthesis pass · year-by-year structured walk · 22 steps
  1. 1994 Medium

    Established the gene product as a human RecQ-family ATP-dependent DNA helicase and placed it in the nucleus, defining the basic biochemical and spatial identity from which all later mechanistic work proceeded.

    Evidence cDNA cloning, reticulocyte lysate expression, and immunofluorescence with antipeptide antibodies in human fibroblasts

    PMID:7961977

    Open questions at the time
    • No substrate polarity or cofactor requirements defined
    • Nuclear import mechanism not yet addressed
  2. 1997 Medium

    Identified how the helicase reaches the nucleus, showing its NLS engages specific importin-alpha homologs.

    Evidence Yeast two-hybrid, GST pulldown, and co-precipitation with Qip1 and Rch1

    PMID:9168958

    Open questions at the time
    • Functional consequence of import for DNA transactions not tested
    • Single-lab interaction without in vivo nuclear-import rescue
  3. 2002 High

    Defined the core enzymatic parameters—3′→5′ polarity, 3′-ssDNA tail requirement, and specific stimulation by human RPA—establishing RECQL as an RPA-dependent helicase on physiological-length substrates.

    Evidence In vitro helicase assays with recombinant protein, polarity and substrate-length titration, RPA versus E. coli SSB comparison

    PMID:12419808

    Open questions at the time
    • Physical basis of RPA stimulation not yet mapped
    • Cellular substrates unknown
  4. 2004 High

    Linked the RPA dependence to a direct, DNA-independent physical contact with the RPA70 subunit and showed the enzyme self-associates as dimers.

    Evidence Gel filtration, DLS, helicase assays, far-western, ELISA, and co-IP

    PMID:15096578

    Open questions at the time
    • Whether higher-order forms exist in cells not addressed
    • Interaction interface not structurally defined
  5. 2005 High

    Revealed that RECQL is not solely a helicase but also catalyzes ATP-modulated strand annealing and acts as the predominant Holliday-junction branch migrator in human extracts, broadening its repertoire to recombination-intermediate processing.

    Evidence In vitro annealing and branch-migration assays, ATPase-deficient mutants, nuclear extract fractionation, and siRNA-coupled SCE measurement

    PMID:15899892 PMID:16260474

    Open questions at the time
    • Structural determinants of the annealing/unwinding switch undefined
    • In vivo branch-migration substrates not identified
  6. 2005 Medium

    Connected RECQL to mismatch repair by demonstrating reciprocal physical and functional cooperation with MSH2/6 and EXO1.

    Evidence Co-IP from extracts, purified-protein interaction, and reciprocal stimulation assays

    PMID:15886194

    Open questions at the time
    • Cellular MMR phenotype of RECQL loss not established
    • Single-lab functional stimulation
  7. 2006 High

    Provided in vivo proof that RECQL is required for genome stability, with knockout cells showing aneuploidy, breakage, translocations, and radiation hypersensitivity.

    Evidence Mouse knockout with cytogenetics, γ-H2AX, SCE, and irradiation-sensitivity assays in MEFs

    PMID:17158923

    Open questions at the time
    • Molecular lesion underlying instability not pinpointed
    • Specific repair pathway requiring RECQL not isolated
  8. 2007 High

    Explained the dual enzymatic behavior structurally by showing quaternary state dictates activity—lower-order oligomers unwind while higher-order oligomers anneal—and that ATP shifts the equilibrium.

    Evidence Size-exclusion chromatography, EM with 3D reconstruction, and ATPase-deficient mutant competition

    PMID:17227144

    Open questions at the time
    • Which oligomeric form predominates in cells not resolved
    • Trigger controlling oligomer interconversion in vivo unknown
  9. 2007 High

    Embedded RECQL in the DNA-damage response, demonstrating damage-induced foci, phosphorylation, RAD51 interaction, and that depletion sensitizes cells to IR and camptothecin.

    Evidence siRNA knockdown, colony survival, immunofluorescence foci, SCE, co-IP, and direct binding assays

    PMID:18074021

    Open questions at the time
    • Kinase responsible for RECQL phosphorylation not identified
    • Functional role of RAD51 interaction not dissected
  10. 2008 High

    Distinguished RECQL from BLM functionally and mapped the N-terminus as essential for oligomerization and unique immobile-Holliday-junction resolution and D-loop disruption.

    Evidence In vitro helicase/branch-migration/D-loop assays with diverse substrates and N-terminal deletion mutagenesis

    PMID:18448429 PMID:18495662

    Open questions at the time
    • In vivo relevance of D-loop disruption not shown
    • Why RECQL cannot regress forks like BLM not mechanistically explained
  11. 2010 High

    Defined a direct role in normal replication, showing cell-cycle-regulated origin loading and that RECQL depletion impairs origin firing and fork rates, and structurally identified the WH-domain β-hairpin (Y564) controlling oligomerization and catalysis.

    Evidence ChIP at origins, DNA fiber analysis, BrdU incorporation, plus full-length mutagenesis with SEC/AUC and functional assays

    PMID:19151156 PMID:20065033 PMID:21059676

    Open questions at the time
    • Mechanism of origin recruitment not defined
    • Tetramer-versus-dimer choice at forks in cells unresolved
  12. 2012 Medium

    Established a PARP1 association and stress-specific recruitment, and showed RECQL acts at stalled forks (leading-strand unwinding, strand exchange) with depletion activating Chk1 and RPA hyperphosphorylation.

    Evidence Co-IP, direct binding, PARP activity and chromatin-recruitment assays under oxidative stress; in vitro fork strand-exchange and knockdown phenotyping

    PMID:22356911 PMID:22542292 PMID:23095637

    Open questions at the time
    • Directionality of PARP1–RECQL regulation not yet established
    • Single-lab functional assays
  13. 2013 High

    Resolved the PARP1–RECQL relationship as a regulatory axis at reversed forks: RECQL restarts TOP1-induced reversed forks while PARP1 PARylation stabilizes the regressed state and limits restart; also tied RECQL to NHEJ via Ku70/80 and to fragile-site stability.

    Evidence Biochemical restart assays, EM of replication intermediates, single-molecule DNA fiber analysis with PARP inhibitors; Ku co-IP and cell-free end-joining; ChIP at FRA3B/FRA16D with aphidicolin sensitivity

    PMID:23396353 PMID:23601052 PMID:23650516

    Open questions at the time
    • How PARylation physically blocks RECQL access undefined
    • In vivo contribution of RECQL to NHEJ versus HR not quantified
  14. 2014 Medium

    Extended RECQL function to telomere maintenance and broadened its biochemical partnerships—TRF2/POT1-regulated activity on telomeric substrates, FEN-1 stimulation, RPA-stimulated protein displacement—and revealed a helicase-dependent transcriptional role at G4-containing promoters.

    Evidence Telomere ChIP, in vitro D-loop/HJ resolution, co-IP, helicase-stimulation and protein-displacement assays; expression profiling with G4-promoter ChIP and helicase-dead rescue

    PMID:24623817 PMID:24895130 PMID:25483193 PMID:25774876

    Open questions at the time
    • Direct versus indirect contribution to telomere transactions in vivo unresolved
    • Mechanistic link between G4 unwinding and transcription not fully defined
  15. 2015 High

    Provided structural mechanism by capturing RECQL bound to tailed-duplex and ssDNA, mapping tail and branch-point contacts and a C-terminal duplex-binding surface, and visualized a flat homotetramer proposed for HJ recognition; functionally linked catalytic mutants to RPA-availability control during replication.

    Evidence X-ray crystallography of DNA complexes, EM, AUC, plus aromatic-loop mutagenesis with DNA fiber analysis, DSB quantification, and RPA-rescue experiments

    PMID:25831490 PMID:26455304

    Open questions at the time
    • Tetramer-HJ recognition not captured at atomic resolution
    • How RECQL globally regulates RPA pools mechanistically unclear
  16. 2016 Medium

    Pinpointed the zinc-binding RQC cysteines as essential for ATPase and unwinding (but not annealing or DNA binding), defining the structural element later implicated in disease.

    Evidence Mutagenesis of conserved cysteines with ATPase, helicase, binding, annealing assays, zinc-content measurement, and limited proteolysis

    PMID:27248010

    Open questions at the time
    • Cellular consequence of zinc-motif disruption not tested at the time
    • Single-lab characterization
  17. 2017 Medium

    Connected RECQL to chemoresistance, showing PARP1 interaction in myeloma, protection against melphalan/bortezomib, and synthetic sensitization to PARP inhibition upon depletion.

    Evidence Co-IP, siRNA knockdown with DSB markers, drug-sensitivity and overexpression-rescue assays in multiple myeloma cells

    PMID:28186131

    Open questions at the time
    • Whether PARP-inhibitor synergy generalizes beyond myeloma unknown
    • Single-lab study
  18. 2019 Medium

    Defined RECQL's role in checkpoint signaling and replication-stress survival, showing it is required for ATR/Chk1 activation after gemcitabine and acts genetically with MUS81.

    Evidence CRISPR/Cas9 knockout, ATR/Chk1 phosphorylation and DSB assays, drug sensitivity, and MUS81 epistasis

    PMID:31444271

    Open questions at the time
    • Mechanism by which RECQL promotes ATR/Chk1 activation undefined
    • Single-lab epistasis
  19. 2020 Medium

    Established that RECQL is specifically essential under replication stress, protecting stalled forks from MRE11-dependent breakage.

    Evidence shRNA genetic screen, RECQL knockdown, γH2AX/DSB assays, MRE11 epistasis, and DNA fiber analysis in cancer cells

    PMID:32820027

    Open questions at the time
    • How RECQL shields nascent DNA from MRE11 mechanistically unclear
    • Single-lab study
  20. 2021 Medium

    Challenged the oligomer model by showing monomeric RECQL predominates in cells and is the most active form, including efficient intramolecular G4 unfolding, and mapped a zinc-binding/WH α-helix that switches between unwinding and annealing; also defined a helicase-dependent FOXA1-cooperative chromatin-opening role at ESR1.

    Evidence Endogenous protein purification with monomer/oligomer activity comparison and G4 assays; crystallography of D2-Zn-WH fragment with mutagenesis; ChIP-seq/ATAC-seq with helicase-dead rescue

    PMID:33468559 PMID:34496242 PMID:34751402

    Open questions at the time
    • Reconciliation of monomer-active model with prior tetramer-HJ data incomplete
    • Generality of transcriptional role across cell types not established
  21. 2022 High

    Demonstrated that RECQL is a Mendelian disease gene, with biallelic zinc-domain p.A459S causing RECON syndrome by selectively crippling ATPase, helicase, and fork restoration while sparing annealing, explaining the cellular topoisomerase-poison repair defect.

    Evidence Patient genetics, recombinant mutant biochemistry (ATPase, helicase, fork restart), and cellular TOP1-poison sensitivity and replication-progression assays

    PMID:35025765

    Open questions at the time
    • Tissue-specific basis of progeroid phenotype unexplained
    • Why annealing-sparing yet pathogenic not fully reconciled
  22. 2025 High

    Delivered atomic-resolution mechanism of G4 and duplex unwinding, showing DNA-induced closed-to-open rearrangement and β-hairpin/ARL-coupled ATP-driven strand separation.

    Evidence Multiple X-ray structures with G4 and duplex DNA, ATP-hydrolysis analysis, and engineered GS-linker construct with mutagenesis and functional assays

    PMID:40512545 PMID:40966504

    Open questions at the time
    • Conformational cycle observed in engineered constructs not validated for native dynamics
    • Coupling of these motions to cellular fork events not shown

Open questions

Synthesis pass · forward-looking unresolved questions
  • How chromatin context controls the PARP1–RECQL fork-restart axis and how RECQL's competing activities (unwinding, annealing, branch migration, G4 resolution) are selected in vivo at specific genomic loci remain open.
  • In vivo determinants of activity-mode selection unknown
  • Chromatin-level regulation (Lamin A/C, H3K9me3) of PAR-dependent restart only shown in preprint
  • Causal chain from molecular defect to RECON progeroid phenotype unestablished

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140657 ATP-dependent activity 5 GO:0140097 catalytic activity, acting on DNA 4 GO:0003677 DNA binding 3 GO:0016787 hydrolase activity 2 GO:0140110 transcription regulator activity 2
Localization
GO:0000228 nuclear chromosome 3 GO:0005634 nucleus 2
Pathway
R-HSA-73894 DNA Repair 4 R-HSA-69306 DNA Replication 3 R-HSA-1640170 Cell Cycle 2 R-HSA-74160 Gene expression (Transcription) 2 R-HSA-1643685 Disease 1
Partners
EXO1FEN1MSH2PARP1RAD51RPA1TERF2XRCC6

Evidence

Reading pass · 38 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1994 RECQL encodes a 659-amino-acid ATP-dependent DNA helicase homologous to E. coli RecQ, localized predominantly to the nucleus of human fibroblasts, as confirmed by antibodies against synthetic N- and C-terminal peptides. cDNA cloning, reticulocyte lysate expression, immunofluorescence with antipeptide antibodies The Journal of biological chemistry Medium 7961977
1997 RECQL physically interacts with importin-alpha homologs Qip1 and Rch1 (but not hSrp1) through its putative NLS, establishing a mechanism for its nuclear import. Yeast two-hybrid screening, GST pulldown, co-precipitation from cell lysates Biochemical and biophysical research communications Medium 9168958
2002 RECQ1 unwinds DNA with 3′ to 5′ polarity, requires a 3′ single-stranded tail >10 nt to initiate unwinding, and its helicase activity on long substrates (>30 bp) is specifically stimulated by human RPA but not E. coli SSB. In vitro helicase assay with recombinant protein, polarity determination, substrate-length titration, SSB specificity comparison The Journal of biological chemistry High 12419808
2004 RECQL1 forms dimers in solution (~158 kDa by gel filtration/DLS), unwinds short duplexes alone, requires hRPA for longer substrates, and directly binds the 70 kDa subunit of hRPA in a DNA-independent manner. Gel filtration, dynamic light scattering, in vitro helicase assay, far-western, ELISA, co-immunoprecipitation Nucleic acids research High 15096578
2005 RECQ1 catalyzes efficient strand annealing between complementary ssDNA molecules; ATP binding induces a conformational change that modulates this annealing activity, distinguishing it from the helicase mode. In vitro strand annealing assay, ATPase-deficient mutant analysis, DNA-binding assays with diverse substrates The Journal of biological chemistry High 15899892
2005 RECQ1 physically interacts with mismatch repair proteins MSH2/6 and exonuclease 1 in vivo (co-IP) and in vitro (purified proteins); MSH2/6 stimulates RECQ1 helicase activity and RECQ1 stimulates EXO1 incision activity. Co-immunoprecipitation from cell extracts, purified protein interaction assays, functional stimulation assays The Journal of biological chemistry Medium 15886194
2005 RecQL1 is the predominant ATP-dependent Holliday junction branch migrator in human nuclear extracts; RNAi-mediated depletion of RecQL1 in HeLa cells increases sister chromatid exchange frequency. Nuclear extract fractionation, in vitro branch migration assay, siRNA knockdown with SCE measurement Nucleic acids research High 16260474
2006 RECQL-deficient mouse embryonic fibroblasts display aneuploidy, spontaneous chromosomal breakage, frequent translocations, hypersensitivity to ionizing radiation, elevated DNA damage load, and increased spontaneous SCEs, demonstrating a unique role in genomic stability. Mouse knockout, cytogenetic analysis, γ-H2AX assay, SCE assay, irradiation sensitivity assay Molecular and cellular biology High 17158923
2007 Different quaternary structures of RECQ1 are associated with distinct enzymatic activities: higher-order oligomers (pentamers/hexamers) favor strand annealing, while lower-order oligomers (monomers/dimers) are required for DNA unwinding; ATP/ATPγS shifts equilibrium toward lower-order forms. Size exclusion chromatography, transmission electron microscopy, 3D EM reconstruction, ATPase-deficient mutant competition assays PLoS biology High 17227144
2007 Human RECQ1 depletion renders cells sensitive to ionizing radiation and camptothecin, causes spontaneous γ-H2AX foci and elevated SCEs, and RECQ1 forms irradiation-induced nuclear foci, becomes phosphorylated upon DNA damage, and directly interacts with RAD51. siRNA knockdown, colony survival assay, immunofluorescence (γ-H2AX, RECQ1 foci), SCE assay, co-immunoprecipitation, direct protein interaction assay PloS one High 18074021
2008 RECQ1 has distinct substrate specificity from BLM: it cannot unwind G-quadruplexes or RNA-DNA hybrids, cannot substitute for BLM in model replication fork regression, but uniquely resolves immobile Holliday junctions lacking a homologous core; the N-terminal region (residues 1–56) is essential for oligomerization and HJ disruption activity. In vitro helicase assay with diverse substrates, N-terminal deletion mutagenesis, substrate competition assays The Journal of biological chemistry High 18448429
2008 RECQ1 efficiently catalyzes unidirectional 3′→5′ DNA branch migration and disrupts D-loops formed by 5′-invading strands, representing a dead-end intermediate of homologous recombination. In vitro branch migration assay with synthetic substrates, D-loop disruption assay, polarity determination The Journal of biological chemistry High 18495662
2009 Crystal structure of truncated human RECQ1 with Mg-ADP reveals conservation of all structural domains (RecA-like, zinc-binding, winged-helix) with distinct WH domain orientation versus E. coli RecQ; a prominent β-hairpin in the WH domain is identified as essential for DNA strand separation. X-ray crystallography, β-hairpin mutant functional analysis Proceedings of the National Academy of Sciences of the United States of America High 19151156
2010 The β-hairpin (with Y564 at tip) in the WH domain of RECQ1 is required for DNA unwinding, HJ resolution activity, dimer formation of truncated RECQ1, and tetramer formation of full-length RECQ1; tetramers are necessary for HJ resolution and strand annealing, while dimers favor DNA unwinding. Site-directed mutagenesis of full-length RECQ1, in vitro helicase/HJ/annealing assays, SEC/analytical ultracentrifugation Nucleic acids research High 21059676
2010 RECQ1 (and RECQ4) associate with replication origins in a cell cycle-regulated manner in unperturbed cells; RECQ1 is loaded at origins at onset of S phase, and its depletion reduces nascent origin DNA synthesis, origin firing frequency, and replication fork rates. ChIP at characterized replication origins, DNA fiber analysis, siRNA depletion, BrdU incorporation assay Molecular and cellular biology High 20065033
2012 RECQ1 associates with PARP-1 in nuclear extracts and directly interacts with PARP-1 in vitro; RECQ1-deficient cells specifically hyperactivate PARP in response to H₂O₂ (but not in undamaged cells), and RECQ1 rapidly and reversibly recruits to chromatin upon oxidative stress before WRN. Co-immunoprecipitation, direct protein interaction assay, PARP activity measurement, chromatin fractionation/localization DNA repair Medium 22542292
2012 RECQ1 promotes strand exchange on synthetic stalled replication fork structures; it unwinds the leading strand of the fork (similar to WRN); stable RECQ1 depletion activates Chk1, hyper-phosphorylates RPA32, and causes chromosome condensation defects. In vitro strand exchange assay with fork substrates, siRNA knockdown, phospho-Chk1/RPA Western blot, chromosomal condensation analysis Cell cycle (Georgetown, Tex.) Medium 23095637
2012 RAD54, BLM, and RECQ1 promote branch migration preferentially in the 3′→5′ direction relative to the displaced ssDNA strand; helicase activity of BM proteins does not play a role in heterology bypass during branch migration. In vitro branch migration assay with RAD51/RecA-made joint molecules, polarity determination, heterology bypass assay The Journal of biological chemistry Medium 22356911
2013 RECQ1 is required for restart of TOP1-inhibitor-induced reversed replication forks; PARP1 poly(ADP-ribosyl)ation stabilizes forks in the regressed state and limits their restart by RECQ1, establishing a PARP1–RECQ1 regulatory axis at stalled forks. Biochemical fork restart assay, electron microscopy of replication intermediates, single-molecule DNA fiber analysis, PARP inhibitor treatment Nature structural & molecular biology High 23396353
2013 RECQ1 directly interacts with Ku70/80 (subunit of DNA-PK); RECQ1 depletion reduces DNA end-joining in cell-free extracts; RECQ1 unwinds Ku70/80-bound partial duplex DNA and modulates Ku70/80 DNA binding, implicating RECQ1 in NHEJ. Co-immunoprecipitation, purified protein binding assay, cell-free end-joining assay, in vitro helicase assay with Ku-bound substrates PloS one Medium 23650516
2013 RECQ1 is specifically enriched at common fragile sites FRA3B and FRA16D under replication stress (aphidicolin treatment); RECQ1 depletion attenuates checkpoint activation, increases aphidicolin sensitivity, and causes chromosomal instability, implicating RECQ1 in repair at stalled forks at fragile sites. ChIP-qPCR at defined replication origins and fragile sites, siRNA knockdown, aphidicolin sensitivity assay, chromosomal instability analysis Molecular cancer Medium 23601052
2014 RECQL1 associates with telomeres in ALT cells, resolves telomeric D-loops and HJ substrates in vitro, physically and functionally interacts with TRF2 (which regulates its helicase activity on telomeric substrates), and is stimulated by POT1 on telomeric substrates with thymine glycol lesions; RECQL1 loss causes telomere dysfunction, shortening, and elevated T-SCEs. ChIP at telomeres, in vitro D-loop/HJ resolution assays, co-immunoprecipitation, helicase stimulation assay, telomere FISH/TIF analysis Nucleic acids research High 24623817
2014 RECQ1 directly interacts with FEN-1 in nuclear extracts and in vitro; recombinant RECQ1 stimulates FEN-1 endonucleolytic cleavage of 5′-flap DNA substrates including telomeric sequences; RECQ1 depletion reduces FEN-1 binding to telomeres. Co-immunoprecipitation, direct protein interaction assay, in vitro FEN-1 stimulation assay, ChIP at telomeres The Biochemical journal Medium 25774876
2014 RPA stimulates RECQ1 (as well as FANCJ) to displace protein-DNA complexes (BamHI-E111A and TRF1/TRF2 from telomeric substrates) in an ATPase-dependent manner; this RPA-stimulated protein displacement is a conserved functional interaction. In vitro protein displacement assay with purified components, ATPase-deficient mutant, RPA vs. SSB specificity comparison The Journal of biological chemistry Medium 24895130
2014 RECQ1 knockdown alters expression of genes promoting cell migration/invasion (including EZR, ITGAs, SMAD3, TGFBR2); RECQ1 binds G4 motifs in promoters of downregulated genes (ChIP); rescue of mRNA expression requires wild-type RECQ1 helicase activity. Genome-wide expression profiling after RECQ1 knockdown, pathway analysis, ChIP with anti-RECQ1, helicase-dead mutant rescue Cell cycle (Georgetown, Tex.) Medium 25483193
2015 Crystal structures of RECQ1 in complex with tailed-duplex DNA and ssDNA map ssDNA tail and branch-point interactions along helicase and Zn-binding domains; a duplex DNA-binding surface on the C-terminal domain contributes to unwinding, strand annealing, and HJ branch migration; EM shows a flat homotetrameric complex proposed to recognize HJs. X-ray crystallography of DNA complexes, EM, analytical ultracentrifugation, functional assays Proceedings of the National Academy of Sciences of the United States of America High 25831490
2015 Aromatic loop (AL) mutants W227A and F231A of full-length RECQ1 are defective in helicase or branch migration but retain ATPase, DNA binding, oligomerization, and strand annealing; expression of these mutants in RECQ1-depleted cells reduces replication tract length, elevates dormant origin firing, and causes DSBs suppressible by exogenous RPA, showing RECQ1 governs RPA availability for normal replication. Site-directed mutagenesis, in vitro biochemical assays (helicase, BM, ATPase, strand annealing), DNA fiber analysis, DSB quantification, RPA rescue experiment Current biology : CB High 26455304
2016 Zinc-binding motif cysteine residues (in RQC domain) are essential for RECQ1 ATPase and DNA unwinding activities and maintain overall protein conformation (zinc coordination, global structure); substitution of three conserved cysteines severely impairs these activities while retaining DNA binding and strand annealing. Site-directed mutagenesis of zinc-binding cysteines, ATPase assay, helicase assay, DNA binding assay, strand annealing assay, zinc content measurement, limited proteolysis Mutation research Medium 27248010
2017 RECQ1 interacts with PARP1 in multiple myeloma cells; RECQ1 depletion promotes DNA DSB formation (53BP1 foci, pATM, γH2AX); RECQ1 overexpression protects cells from melphalan and bortezomib; RECQ1 depletion sensitizes cells to PARP inhibitor. Co-immunoprecipitation, siRNA knockdown with γH2AX/53BP1/pATM readout, drug sensitivity assay, overexpression rescue Leukemia Medium 28186131
2019 RECQ1 loss leads to defective ATR/Chk1 checkpoint activation in response to gemcitabine; dual deficiency of MUS81 and RECQ1 increases replication-associated DSBs; Chk1 inhibitor further sensitizes RECQ1-deficient cells to gemcitabine. CRISPR/Cas9 knockout, Chk1/ATR phosphorylation assay, DSB assay, drug sensitivity assay, genetic epistasis (MUS81/RECQ1 double deficiency) The Journal of biological chemistry Medium 31444271
2021 RECQ1 expression activates ESR1 (ERα) gene; >35% of RECQ1 chromatin-binding sites are co-bound by ERα; RECQ1 cooperates with pioneer factor FOXA1 to enhance chromatin accessibility at ESR1 regulatory regions in a helicase activity-dependent manner. ChIP-seq, ATAC-seq, gene expression analysis after RECQ1 knockdown, helicase-dead mutant rescue Molecular and cellular biology Medium 33468559
2021 Monomeric RECQ1 is the predominant form in living cells (Bos taurus) and is more active (higher helicase and ATPase activities) than dimers or oligomers; monomeric RECQ1 efficiently unfolds intramolecular G-quadruplex DNA. Endogenous protein purification and characterization, cell fractionation, helicase/ATPase assays comparing monomer vs. oligomer, G4 unfolding assay Cell reports Medium 34496242
2021 An α-helix in the zinc-binding domain of RECQ1 interacts with residues in the WH domain; deletion or mutation of this α-helix restores strand annealing activity in annealing-deficient RECQ1 constructs and induces conformational changes affecting ATPase and unwinding activities, revealing that the zinc-binding/WH domain interface controls the switch between unwinding and annealing modes. X-ray crystallography of D2-Zn-WH fragment, site-directed mutagenesis, strand annealing assay, ATPase assay, helicase assay Nucleic acids research Medium 34751402
2022 Biallelic missense mutation p.A459S in the RECQL1 zinc-binding domain causes RECON syndrome (progeroid features, xeroderma, photosensitivity); biochemically, p.A459S compromises ATPase, helicase, and fork restoration activity while strand annealing is largely unaffected; RECON patient cells are defective in repair of topoisomerase-poison-induced DNA damage and fail to support replication progression through abortive TOP1 lesions. Patient genetics, recombinant mutant protein biochemical assays (ATPase, helicase, fork restart), cellular repair assay (TOP1 poison sensitivity, replication progression) The Journal of clinical investigation High 35025765
2025 Crystal structures of RECQ1 in complex with G-quadruplex DNA reveal that DNA binding induces an intra-subunit closed-to-open conformational rearrangement; G4 recognition involves coordinated D1/D2 domain and ssDNA-binding channel interactions; ATP hydrolysis drives ssDNA translocation and β-hairpin-mediated unraveling of G4 tetrad hydrogen bonds analogously to dsDNA unwinding. X-ray crystallography (five structures with G4 and duplex DNA), structural comparison, ATP hydrolysis analysis Nucleic acids research High 40966504
2025 An engineered RECQ1 with a flexible GS-linker between zinc-binding and WH domains shows that WH domain repositioning and ARL coordination remodel the ATPase domain; crystal structure with DNA shows a compact conformation where β-hairpin tip proximity to the aromatic-rich loop (ARL) enhances DNA binding and strand separation, coupling ATP hydrolysis to unwinding. X-ray crystallography of engineered RECQ1-DNA complex, site-directed mutagenesis, helicase/DNA-binding assays Nucleic acids research Medium 40512545
2020 RECQL helicase is specifically essential under replication stress conditions and protects stalled replication forks against MRE11-dependent DSB formation; RECQL knockdown in cancer cells increases DSB levels under replication stress. shRNA genetic screen, RECQL knockdown, γH2AX/DSB assay, MRE11 epistasis, DNA fiber analysis Life science alliance Medium 32820027
2025 Nucleoplasmic Lamin A/C and H3K9me3 at stalled forks are required to maintain poly-ADP-ribosylation at nascent DNA; loss of Lamin A/C or H3K9me3 reduces PAR levels and deregulates RECQ1-mediated restart of reversed replication forks. Acute protein inactivation (auxin-inducible degron), single-molecule DNA fiber analysis, PAR level measurement at nascent DNA, RECQ1 fork restart assay, H3K9me3 ChIP bioRxivpreprint Medium

Source papers

Stage 0 corpus · 88 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2013 Human RECQ1 promotes restart of replication forks reversed by DNA topoisomerase I inhibition. Nature structural & molecular biology 398 23396353
1984 Isolation and genetic characterization of a thymineless death-resistant mutant of Escherichia coli K12: identification of a new mutation (recQ1) that blocks the RecF recombination pathway. Molecular & general genetics : MGG 221 6381965
1994 Cloning and characterization of RECQL, a potential human homologue of the Escherichia coli DNA helicase RecQ. The Journal of biological chemistry 179 7961977
2003 Molecular defect of RAPADILINO syndrome expands the phenotype spectrum of RECQL diseases. Human molecular genetics 155 12952869
2015 Germline RECQL mutations are associated with breast cancer susceptibility. Nature genetics 152 25915596
2005 Biochemical analysis of the DNA unwinding and strand annealing activities catalyzed by human RECQ1. The Journal of biological chemistry 149 15899892
2008 The Human RecQ helicases, BLM and RECQ1, display distinct DNA substrate specificities. The Journal of biological chemistry 132 18448429
2006 Single nucleotide polymorphisms of RecQ1, RAD54L, and ATM genes are associated with reduced survival of pancreatic cancer. Journal of clinical oncology : official journal of the American Society of Clinical Oncology 123 16520463
2010 Human RECQ1 and RECQ4 helicases play distinct roles in DNA replication initiation. Molecular and cellular biology 120 20065033
2009 Structure of the human RECQ1 helicase reveals a putative strand-separation pin. Proceedings of the National Academy of Sciences of the United States of America 109 19151156
2004 Analysis of the unwinding activity of the dimeric RECQ1 helicase in the presence of human replication protein A. Nucleic acids research 102 15096578
2006 RECQL, a member of the RecQ family of DNA helicases, suppresses chromosomal instability. Molecular and cellular biology 98 17158923
2007 Human RECQ1 is a DNA damage responsive protein required for genotoxic stress resistance and suppression of sister chromatid exchanges. PloS one 89 18074021
1997 Cloning of a cDNA encoding a novel importin-alpha homologue, Qip1: discrimination of Qip1 and Rch1 from hSrp1 by their ability to interact with DNA helicase Q1/RecQL. Biochemical and biophysical research communications 82 9168958
2005 RECQ1 helicase interacts with human mismatch repair factors that regulate genetic recombination. The Journal of biological chemistry 80 15886194
2003 Functional relation among RecQ family helicases RecQL1, RecQL5, and BLM in cell growth and sister chromatid exchange formation. Molecular and cellular biology 80 12724411
2015 Mutations in RECQL Gene Are Associated with Predisposition to Breast Cancer. PLoS genetics 79 25945795
2002 Characterization of the DNA-unwinding activity of human RECQ1, a helicase specifically stimulated by human replication protein A. The Journal of biological chemistry 67 12419808
2017 RECQ1 helicase is involved in replication stress survival and drug resistance in multiple myeloma. Leukemia 66 28186131
2008 RECQ1 possesses DNA branch migration activity. The Journal of biological chemistry 62 18495662
2011 RECQL1 and WRN proteins are potential therapeutic targets in head and neck squamous cell carcinoma. Cancer research 58 21571861
2007 Different quaternary structures of human RECQ1 are associated with its dual enzymatic activity. PLoS biology 57 17227144
2010 A prominent β-hairpin structure in the winged-helix domain of RECQ1 is required for DNA unwinding and oligomer formation. Nucleic acids research 56 21059676
2015 Human RECQ1 helicase-driven DNA unwinding, annealing, and branch migration: insights from DNA complex structures. Proceedings of the National Academy of Sciences of the United States of America 53 25831490
2011 The human RECQ1 helicase is highly expressed in glioblastoma and plays an important role in tumor cell proliferation. Molecular cancer 48 21752281
2012 RECQ1 plays a distinct role in cellular response to oxidative DNA damage. DNA repair 47 22542292
2013 Human RECQ1 interacts with Ku70/80 and modulates DNA end-joining of double-strand breaks. PloS one 46 23650516
2005 Identification of RecQL1 as a Holliday junction processing enzyme in human cell lines. Nucleic acids research 45 16260474
2008 Anticancer activity of RecQL1 helicase siRNA in mouse xenograft models. Cancer science 44 18422747
2012 RECQ1 is required for cellular resistance to replication stress and catalyzes strand exchange on stalled replication fork structures. Cell cycle (Georgetown, Tex.) 43 23095637
2007 Induction of mitotic cell death in cancer cells by small interference RNA suppressing the expression of RecQL1 helicase. Cancer science 43 17953710
2014 Human RECQL1 participates in telomere maintenance. Nucleic acids research 39 24623817
2008 Unique and important consequences of RECQ1 deficiency in mammalian cells. Cell cycle (Georgetown, Tex.) 38 18414032
2022 RECON syndrome is a genome instability disorder caused by mutations in the DNA helicase RECQL1. The Journal of clinical investigation 35 35025765
2014 Identification of RECQ1-regulated transcriptome uncovers a role of RECQ1 in regulation of cancer cell migration and invasion. Cell cycle (Georgetown, Tex.) 35 25483193
2013 Replication stress induces specific enrichment of RECQ1 at common fragile sites FRA3B and FRA16D. Molecular cancer 35 23601052
2015 Catalytic strand separation by RECQ1 is required for RPA-mediated response to replication stress. Current biology : CB 32 26455304
2014 Novel function of the Fanconi anemia group J or RECQ1 helicase to disrupt protein-DNA complexes in a replication protein A-stimulated manner. The Journal of biological chemistry 32 24895130
2015 RECQL1 and WRN DNA repair helicases: potential therapeutic targets and proliferative markers against cancers. Frontiers in genetics 30 25620975
2010 Distinct roles of RECQ1 in the maintenance of genomic stability. DNA repair 30 20061189
2012 Polarity and bypass of DNA heterology during branch migration of Holliday junctions by human RAD54, BLM, and RECQ1 proteins. The Journal of biological chemistry 26 22356911
2020 RECQ1 Helicase in Genomic Stability and Cancer. Genes 23 32517021
2016 Germline RECQL mutations in high risk Chinese breast cancer patients. Breast cancer research and treatment 23 27125668
2018 FANCM and RECQL genetic variants and breast cancer susceptibility: relevance to South Poland and West Ukraine. BMC medical genetics 21 29351780
2017 Analysis of a RECQL splicing mutation, c.1667_1667+3delAGTA, in breast cancer patients and controls from Central Europe. Familial cancer 20 27832498
2014 An appraisal of RECQ1 expression in cancer progression. Frontiers in genetics 20 25538733
2013 RECQL1 DNA repair helicase: a potential therapeutic target and a proliferative marker against ovarian cancer. PloS one 20 23951333
2019 The DNA repair helicase RECQ1 has a checkpoint-dependent role in mediating DNA damage responses induced by gemcitabine. The Journal of biological chemistry 19 31444271
1995 Chromosomal localization of the gene encoding the human DNA helicase RECQL and its mouse homologue. Genomics 19 7607686
2013 Probing Genome Maintenance Functions of human RECQ1. Computational and structural biotechnology journal 18 24688722
2015 RECQ1 interacts with FEN-1 and promotes binding of FEN-1 to telomeric chromatin. The Biochemical journal 17 25774876
2009 Topoisomerase I and RecQL1 function in Epstein-Barr virus lytic reactivation. Journal of virology 17 19494003
2018 Rare missense mutations in RECQL and POLG associate with inherited predisposition to breast cancer. International journal of cancer 16 29341116
2016 Transcriptome guided identification of novel functions of RECQ1 helicase. Methods (San Diego, Calif.) 16 27102625
2016 Clinicopathological and Functional Significance of RECQL1 Helicase in Sporadic Breast Cancers. Molecular cancer therapeutics 16 27837030
2021 Endogenous Bos taurus RECQL is predominantly monomeric and more active than oligomers. Cell reports 15 34496242
1998 Cloning of two isoforms of mouse DNA helicase Q1/RecQL cDNA; alpha form is expressed ubiquitously and beta form specifically in the testis. Biochimica et biophysica acta 15 9838113
2009 Single nucleotide polymorphism in RECQL and survival in resectable pancreatic adenocarcinoma. HPB : the official journal of the International Hepato Pancreato Biliary Association 14 19768149
2019 Clinical implications of germline mutations in breast cancer genes: RECQL. Breast cancer research and treatment 13 30610487
2019 DNA helicase RecQ1 regulates mutually exclusive expression of virulence genes in Plasmodium falciparum via heterochromatin alteration. Proceedings of the National Academy of Sciences of the United States of America 13 30728298
2015 RECQL: a new breast cancer susceptibility gene. Cell cycle (Georgetown, Tex.) 13 26125302
2022 Non-enzymatic function of WRN RECQL helicase regulates removal of topoisomerase-I-DNA covalent complexes and triggers NF-κB signaling in cancer. Aging cell 12 35582959
2017 RECQ1 Helicase Silencing Decreases the Tumour Growth Rate of U87 Glioblastoma Cell Xenografts in Zebrafish Embryos. Genes 12 28878163
2017 RECQ1 expression is upregulated in response to DNA damage and in a p53-dependent manner. Oncotarget 11 29100281
2007 Analyses of functional interaction between RECQL1, RECQL5, and BLM which physically interact with DNA topoisomerase IIIalpha. Biochimica et biophysica acta 11 18078829
2014 RECQL1 plays an important role in the development of tongue squamous cell carcinoma. Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology 10 24854846
2012 Transcription directed by human core promoters with a HomolD box sequence requires DDB1, RECQL and RNA polymerase II machinery. Gene 9 22705827
2021 Genome-Wide Analysis Unveils DNA Helicase RECQ1 as a Regulator of Estrogen Response Pathway in Breast Cancer Cells. Molecular and cellular biology 8 33468559
2021 RECQ1 Promotes Stress Resistance and DNA Replication Progression Through PARP1 Signaling Pathway in Glioblastoma. Frontiers in cell and developmental biology 8 34381789
2020 Prevalence of RECQL germline variants in Pakistani early-onset and familial breast cancer patients. Hereditary cancer in clinical practice 8 33342430
2020 The RECQL helicase prevents replication fork collapse during replication stress. Life science alliance 6 32820027
2016 Site-directed mutants of human RECQ1 reveal functional importance of the zinc binding domain. Mutation research 6 27248010
2014 Cellular deficiency of Werner syndrome protein or RECQ1 promotes genotoxic potential of hydroquinone and benzo[a]pyrene exposure. International journal of toxicology 5 25228686
2025 Structural mechanism of RECQ1 helicase in unfolding G-quadruplexes compared with duplex DNA. Nucleic acids research 4 40966504
2024 Germline RECQL gene mutations in Chinese patients with breast cancer. Frontiers in medicine 4 38439896
2021 Residues at the interface between zinc binding and winged helix domains of human RECQ1 play a significant role in DNA strand annealing activity. Nucleic acids research 4 34751402
2016 Effects of RECQ1 helicase silencing on non-small cell lung cancer cells. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 4 27565844
2002 Molecular cloning of a splicing variant of human RECQL helicase. Biochemical and biophysical research communications 4 12419324
2023 Case report: Germline RECQL mutation potentially involved in hereditary predisposition to acute leukemia. Frontiers in oncology 3 36998465
2022 Variant Identification in BARD1, PRDM9, RCC1, and RECQL in Patients with Ovarian Cancer by Targeted Next-generation Sequencing of DNA Pools. Cancer prevention research (Philadelphia, Pa.) 3 34906988
2022 Genome-wide investigations on regulatory functions of RECQ1 helicase. Methods (San Diego, Calif.) 3 35231585
2012 In Vitro Enzyme Comparative Kinetics: Unwinding of Surface-Bound DNA Nanostructures by RecQ and RecQ1. The journal of physical chemistry letters 3 26290984
2022 High Expression of RECQL Protein in ER-Positive Breast Tumours Is Associated With a Better Survival. Frontiers in oncology 2 35712517
2019 Allelic variants of breast cancer susceptibility genes PALB2 and RECQL in the Latvian population. Hereditary cancer in clinical practice 2 31312277
2025 Efficient coordination between the winged helix domain and the aromatic-rich loop restructures the ATPase domain and facilitates DNA unwinding by human RECQ1. Nucleic acids research 1 40512545
2025 Association analysis of germline mutations in CHEK2, PALB2, NBN and RECQL with the risk of ductal carcinoma in situ in Polish women. Hereditary cancer in clinical practice 0 40770660
2025 Spindle Cell Spindle Sarcoma Harboring a Novel RECQL::ROS1 Gene Fusion. International journal of surgical pathology 0 40924629
2025 RECQL1 as a potential therapeutic target for PARP inhibitor-resistant ovarian cancer. Scientific reports 0 41168257

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