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Showing RECQL5 — RECQ5 is a alias.

RECQL5

ATP-dependent DNA helicase Q5 · UniProt O94762

Length
991 aa
Mass
108.9 kDa
Annotated
2026-06-10
83 papers in source corpus 36 papers cited in narrative 36 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 7/7 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

RECQL5 is a multifunctional RecQ-family DNA helicase that safeguards genome stability at the interface of DNA replication, repair, and transcription, and its loss in mice causes cancer susceptibility together with spontaneous DSBs, elevated homologous recombination, and replication-stress-induced chromosomal rearrangements (PMID:18003859). In recombination, RECQL5 binds RAD51 and disrupts RAD51 presynaptic filaments on ssDNA in an ATP-hydrolysis- and RPA-dependent manner, inhibiting D-loop formation and suppressing inappropriate recombination (PMID:18003859); single-molecule imaging established it as an ATP-dependent ssDNA translocase that actively dismantles RAD51 filaments, with translocation enhanced by a direct RECQL5-RAD51 interface (PMID:33332547). This RAD51-interaction is mediated by a BRC-repeat-variant (BRCv) domain whose mutation impairs filament disruption, SCE suppression, and camptothecin resistance (PMID:20348101, PMID:22645136), and functionally channels DSB repair toward non-crossover synthesis-dependent strand annealing (SDSA) by counteracting RAD51's inhibition of RAD52-mediated annealing (PMID:24319145), a subpathway choice further partitioned with ATRX through PCNA binding (PMID:33431668). RECQL5 acts genetically in a BLM-independent pathway to suppress sister chromatid exchange (PMID:15831450). In transcription, RECQL5 is the only human RecQ that directly associates with RNA Polymerase II via the RPB1 subunit (PMID:18562274), binding the Ser2,5-phosphorylated CTD through an SRI motif and the Pol II body through a KIX domain (PMID:20705653, PMID:20231364), thereby acting as an elongation roadblock independent of helicase activity (PMID:19570979); cryo-EM structures show RECQL5 contacts the Rpb1 jaw at the TFIIS-binding site and uses a 'brake helix' to control Pol II translocation state, suppressing transcription-coupled repair-mediated Pol II ubiquitination (PMID:23748380, PMID:40624164, PMID:40624163). Loss of RECQL5 produces transcription stress, RNAPII accumulation, and transcription-associated DSBs, linking its elongation control to genome protection (PMID:21402780, PMID:24836610). RECQL5 additionally cooperates with the MRN complex, which recruits it to DSBs and whose MRE11 exonuclease it inhibits (PMID:19270065, PMID:22633600); promotes MUS81-EME1-dependent mitotic DNA synthesis at common fragile sites via CDK1-dependent Ser727 phosphorylation (PMID:28575661); stimulates Topoisomerase IIα decatenation (PMID:22013166) and PIAS1-SRSF1-mediated TOP1 SUMOylation (PMID:25851487); counteracts replication fork stalling and excessive RAD51-driven fork reversal through PCNA binding (PMID:27502483, PMID:41099703); and functions in the nucleolus in pre-rRNA processing, where it recognizes and unwinds pre-rRNA to prevent R-loop-driven ATR activation (PMID:40823811).

Mechanistic history

Synthesis pass · year-by-year structured walk · 16 steps
  1. 2000 Medium

    Established the first cellular and partner context for RECQL5 by showing isoform-specific localization and topoisomerase association, framing the nuclear RecQ5beta isoform as the functionally relevant form.

    Evidence Immunocytochemistry of tagged isoforms and immunoprecipitation in 293EBNA cells

    PMID:10710432

    Open questions at the time
    • Did not assign a biochemical activity to the helicase
    • Topo3alpha/3beta interaction not tied to a pathway
  2. 2005 High

    Resolved whether RECQL5 has a unique anti-recombination role by showing it suppresses crossovers in a pathway genetically separable from BLM.

    Evidence Blm/Recql5 single and double knockout mouse ES cells and MEFs with SCE assay

    PMID:15831450

    Open questions at the time
    • Molecular substrate of suppression not defined
    • Did not establish the biochemical mechanism
  3. 2007 High

    Defined the core anti-recombinase mechanism by demonstrating RECQL5 directly disrupts RAD51 presynaptic filaments and blocks D-loop formation, explaining its HR-suppressive function.

    Evidence Purified-protein D-loop and ssDNA displacement assays, EM, ATPase-mutant controls

    PMID:18003859

    Open questions at the time
    • Translocation versus passive displacement not distinguished
    • RAD51-interaction domain not yet mapped
  4. 2008 High

    Linked RECQL5 to transcription and to tumor suppression in vivo, revealing a second functional axis and disease relevance.

    Evidence Chromatin proteomics and direct interaction assays identifying RPB1 binding; Recql5 knockout mouse tumor and HR analyses

    PMID:18003859 PMID:18562274

    Open questions at the time
    • Interaction interface and elongation consequence not yet defined
    • How transcription role connects to cancer phenotype unresolved
  5. 2009 High

    Established RECQL5's mechanism of transcriptional inhibition and its DSB-recruitment route, separating helicase-independent roadblock function from MRN-mediated targeting.

    Evidence Reconstituted in vitro transcription with interaction-deficient mutant; purified MRN interaction, exonuclease and laser-damage recruitment assays

    PMID:19270065 PMID:19570979

    Open questions at the time
    • CTD-phosphorylation specificity of binding not yet defined
    • Physiological consequence of MRE11 inhibition unclear
  6. 2010 High

    Dissected the bipartite RNAPII engagement (SRI binds elongating Pol IIo CTD; KIX binds both forms) and mapped the RAD51-interacting domain, separating the transcription and recombination interfaces.

    Evidence CTD phospho-variant binding, ChIP, domain mapping and point mutants, ssDNA displacement, HR reporter, complex purification with MS

    PMID:20231364 PMID:20348101 PMID:20705653

    Open questions at the time
    • Structural basis of Pol II contact not yet resolved
    • Whether KIX and helicase act jointly on chromatin unresolved
  7. 2011 High

    Connected the transcription axis to genome stability and identified additional partners, showing SRI-dependent prevention of transcription-associated DSBs and TOP2alpha decatenation stimulation.

    Evidence SRI mutants with RNAPII ChIP and gammaH2AX; transcription-inhibitor epistasis; TOP2alpha decatenation and depletion phenotyping

    PMID:21402780 PMID:22013166

    Open questions at the time
    • Direct cause of breaks (collision vs R-loop) not yet defined
    • TOP2alpha stimulation mechanism uncharacterized
  8. 2012 High

    Defined the BRCv RAD51-interaction module and broadened partner/repair context, mapping recruitment requirements and adding WRN cooperation and BER/SSB involvement.

    Evidence BRCv mutagenesis with D-loop/SCE/drug assays; domain-mutant DSB recruitment imaging; WRN helicase-stimulation and synthetic lethality; laser SSB recruitment and BER protein analysis

    PMID:22633600 PMID:22645136 PMID:22973052 PMID:23180761 PMID:28180303

    Open questions at the time
    • WRN and BER roles rest on single-lab medium-confidence data
    • Hierarchy among recruitment cues unresolved
  9. 2013 High

    Provided structural and pathway-level mechanism, showing RECQL5 sterically blocks elongation by mimicking the Pol II-TFIIS interaction and channels DSB repair toward non-crossover SDSA.

    Evidence Cryo-EM of Pol II-RECQL5 plus KIX crystal structure and read-through assays; HR reporter, in vitro RAD52 annealing, RAD51 ChIP and SCE

    PMID:23748380 PMID:24319145

    Open questions at the time
    • Allosteric basis of translocation control not yet resolved
    • In vivo balance between SDSA and other subpathways unclear
  10. 2014 High

    Demonstrated genome-wide that RECQL5 controls elongation kinetics and that loss causes transcription stress overlapping chromosomal breakpoints, establishing the elongation-roadblock function as protective.

    Evidence RNAPII ChIP-seq, RNA-seq, and copy-number analysis in RECQL5-depleted cells

    PMID:24836610

    Open questions at the time
    • Direct molecular trigger of stress-associated breaks not defined
    • Gene-class selectivity of effect unresolved
  11. 2015 High

    Extended RECQL5's transcription-genome interface to topoisomerase regulation and R-loop control via TOP1 SUMOylation, plus PARP/PAR-dependent damage recruitment.

    Evidence In vivo SUMOylation, ChIP, S9.6 R-loop detection and site mutants; PAR-binding, recruitment imaging and PARP-inhibitor sensitivity

    PMID:25851487 PMID:26391948

    Open questions at the time
    • PARP-dependent recruitment is medium-confidence single-lab
    • Whether SUMOylation control is direct enzymatic or scaffolding unclear
  12. 2016 High

    Connected RECQL5 to replication-transcription conflict resolution, showing it acts at both RNAPI- and RNAPII-transcribed loci via PCNA to promote fork progression and RAD18-dependent PCNA ubiquitination.

    Evidence Co-IP, immunofluorescence, DNA fiber assay, PCNA ubiquitination assay, PCNA-interaction domain mapping

    PMID:27502483

    Open questions at the time
    • Mechanism of intermediate processing not fully defined
    • Relative contribution of helicase vs scaffolding unresolved
  13. 2017 High

    Defined a mitotic, CDK1-regulated role at common fragile sites and refined the helicase mechano-chemical cycle, integrating RAD51 filament disruption into MUS81-EME1-dependent mitotic DNA synthesis.

    Evidence Ser727 phospho-site mutants, MUS81 co-IP, CFS ChIP, in vitro cleavage assays; crystal structures (Open/Closed) with SAXS and activity mutagenesis

    PMID:28100692 PMID:28575661

    Open questions at the time
    • How CDK1 timing coordinates with interphase functions unclear
    • Structural basis of DNA unwinding directionality limited
  14. 2020 Medium

    Showed alternative splicing of the KIX domain tunes RECQL5 between transcription repression and DSB repair, revealing isoform-level functional partitioning.

    Evidence RECQL5β1 isoform binding-affinity, in vitro transcription, MRE11 co-IP, and DNA repair rescue assays

    PMID:33197722

    Open questions at the time
    • Single-lab isoform comparison without in vivo confirmation
    • Physiological abundance/regulation of isoform unknown
  15. 2021 High

    Resolved the filament-disruption mechanism at single-molecule resolution and the DSB subpathway logic, defining RECQL5 as a translocase whose ssDNA-motor activity competes with ATRX-dependent HR via PCNA.

    Evidence Single-molecule TIRF with RAD51 mutants and F666A interface mutant; HR subpathway/SCE assays with ATRX/MUS81/GEN1 epistasis and PCNA-domain analysis

    PMID:33332547 PMID:33431668

    Open questions at the time
    • Inability to dismantle heteroduplex-bound RAD51 leaves post-synaptic limits
    • Coordination of competing PCNA-binding factors not fully defined
  16. 2025 High

    Delivered atomic-level mechanism of RECQL5's transcriptional braking and uncovered a nucleolar pre-rRNA processing role, broadening its genome-protective remit to RNA metabolism.

    Evidence Cryo-EM of stalled Pol II-RECQL5 complexes (brake helix, translocation control, TCR competition and Pol II ubiquitination); nucleolar localization, pre-rRNA co-IP, dsRNA unwinding, Northern blot, R-loop and ATR assays; fork-reversal restriction by fiber/PLA epistasis

    PMID:40624163 PMID:40624164 PMID:40823811 PMID:41099703

    Open questions at the time
    • How nucleolar, transcription and replication functions are temporally partitioned unresolved
    • In vivo significance of TCR-ubiquitination suppression untested

Open questions

Synthesis pass · forward-looking unresolved questions
  • How RECQL5's distinct activities — RAD51 filament disruption, Pol II elongation control, fork-reversal restriction, and pre-rRNA processing — are coordinated, prioritized, and spatially partitioned within a cell remains unresolved.
  • No unified model of how shared modules (helicase, PCNA, RAD51, RNAPII binding) are switched between functions
  • Condensate-scaffold organization rests on preprint-level data
  • Disease mechanism linking specific activity loss to cancer not dissected

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0098772 molecular function regulator activity 4 GO:0060090 molecular adaptor activity 3 GO:0140097 catalytic activity, acting on DNA 3 GO:0140657 ATP-dependent activity 3 GO:0003677 DNA binding 2 GO:0003723 RNA binding 2 GO:0140098 catalytic activity, acting on RNA 1
Localization
GO:0000228 nuclear chromosome 2 GO:0005634 nucleus 2 GO:0005730 nucleolus 2 GO:0005654 nucleoplasm 1
Pathway
R-HSA-73894 DNA Repair 4 R-HSA-74160 Gene expression (Transcription) 4 R-HSA-1640170 Cell Cycle 2 R-HSA-69306 DNA Replication 2 R-HSA-1643685 Disease 1 R-HSA-8953854 Metabolism of RNA 1
Partners
MRE11MUS81NBS1PCNARAD51RPB1 (POLR2A)TOP2AWRN
Complex memberships
MRN (MRE11-RAD50-NBS1) complexRNA Polymerase II elongation complex

Evidence

Reading pass · 36 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2007 RECQL5 binds RAD51 recombinase and inhibits RAD51-mediated D-loop formation; it displaces RAD51 from single-stranded DNA (ssDNA) in a reaction requiring ATP hydrolysis and RPA, thereby disrupting RAD51 presynaptic filaments and suppressing homologous recombination. Purified protein biochemical assays (D-loop formation assay, ssDNA displacement assay), electron microscopy, ATPase mutant analysis Genes & development High 18003859
2008 RECQL5 (RECQ5) is a bona fide RNA polymerase II (RNAPII)-associated protein; the interaction is direct and mediated by the RPB1 subunit of RNAPII; RECQL5 is the only human RECQ family member that associates with RNAPII. Chromatin isolation, targeted proteomic analysis, direct interaction assay with purified proteins, co-immunoprecipitation Proceedings of the National Academy of Sciences of the United States of America High 18562274
2000 The large isoform RecQ5beta localizes exclusively in the nucleoplasm, while small isoforms RecQ5alpha and RecQ5gamma remain cytoplasmic; RecQ5beta interacts with topoisomerases 3alpha and 3beta but not topoisomerase 1. Immunocytochemical staining of tagged isoforms expressed in 293EBNA cells, immunoprecipitation Nucleic acids research Medium 10710432
2005 Recql5 and Blm have nonredundant roles in suppressing crossovers (sister chromatid exchange) in mouse cells; deletion of both Blm and Recql5 leads to an even higher SCE frequency than either single knockout, establishing a Recql5-dependent, Blm-independent pathway for suppressing crossovers during mitosis. Genetic knockout in mouse ES cells and MEFs, sister chromatid exchange assay Molecular and cellular biology High 15831450
2009 RECQL5 inhibits both initiation and elongation of RNAPII-dependent transcription in vitro; this inhibition requires its RNAPII-interaction domain but not its helicase activity. In vitro transcription assay reconstituted with purified general transcription factors and RNAPII, RNAPII-interaction-deficient RECQL5 mutant The Journal of biological chemistry High 19570979
2010 RECQL5 specifically binds the Ser2,5-phosphorylated C-terminal repeat domain (CTD) of RPB1 via a Set2-Rpb1-interacting (SRI) motif at its C-terminus; RECQL5 associates with RNAPII-transcribed genes in an SRI-dependent manner, with density correlating with Ser2-CTD phosphorylation marking productive elongation. Binding assays with CTD phosphorylation variants, chromatin immunoprecipitation (ChIP), SRI deletion/mutation analysis Nucleic acids research High 20705653
2010 RECQL5 interacts with RAD51 through a RAD51-interacting domain; RECQL5 mutants that fail to bind RAD51 retain normal ATPase activity but are impaired in displacing RAD51 from ssDNA, and ablation of RECQL5-RAD51 complex formation alleviates RECQL5's inhibitory effect on HR-mediated DSB repair. Mapping of RAD51-interacting domain, generation of binding-deficient point mutants, in vitro ssDNA displacement assay, HR reporter assay in cells The Journal of biological chemistry High 20348101
2010 RECQL5 interacts with RNAPII through both KIX (binds initiation form Pol IIa and elongation form Pol IIo) and SRI (binds only elongation form Pol IIo) domains; RECQL5 requires both helicase activity and KIX-mediated Pol II interaction for full suppression of sister chromatid exchange and resistance to camptothecin. Purification of RECQL5-associated complex, mass spectrometry identification, structural modeling-guided mutagenesis, SCE assay, drug sensitivity assay Molecular and cellular biology High 20231364
2009 RECQL5 is constitutively associated with the MRE11-RAD50-NBS1 (MRN) complex through direct interactions with both MRE11 and NBS1; RECQL5 specifically inhibits the 3'→5' exonuclease activity of MRE11; the MRN complex is required for recruitment of RECQL5 to sites of DNA damage. Purified protein interaction assays, co-immunoprecipitation, exonuclease activity assay, laser-induced damage recruitment (live cell imaging) Nucleic acids research High 19270065
2011 RECQL5 physically and functionally interacts with Topoisomerase IIα; RECQL5 stimulates the decatenation activity of Topoisomerase IIα in vitro; RECQL5 co-localizes with Topoisomerase IIα during S-phase; RECQL5 depletion causes G2/M arrest, undercondensed/entangled chromosomes, and phenotypes resembling Topoisomerase II inhibition. Direct interaction assay with purified proteins, decatenation assay, co-localization (immunofluorescence), stable knockdown cell lines, cell cycle analysis Nucleic acids research High 22013166
2011 The SRI domain of RECQL5 is important for suppressing spontaneous DSBs and the p53-dependent transcription stress response; in RECQL5-depleted cells, active RNAPII accumulates on chromatin and DNA breaks associate with RNAPII-dependent transcribed loci; transcription inhibition eliminates both RNAPII accumulation and spontaneous DSB formation. SRI domain mutants, RNAPII ChIP, γH2AX foci analysis, transcription inhibitor treatment, p53 reporter assay Molecular and cellular biology High 21402780
2012 RECQL5 contains a BRC repeat variant (BRCv) that mediates interaction with RAD51 through two conserved motifs; mutations in either motif compromise RECQL5's ability to associate with RAD51, inhibit D-loop formation, suppress SCE, and confer resistance to camptothecin-induced replication stress. Identification and mutagenesis of BRCv domain, co-immunoprecipitation, D-loop inhibition assay, SCE assay, drug sensitivity assay The Journal of biological chemistry High 22645136
2013 Cryo-EM structure of elongating Pol II arrested in complex with RECQL5 shows that RECQL5 helicase domain is positioned to sterically block elongation; RECQL5 KIX domain contacts the Rpb1 jaw domain at a site overlapping the TFIIS binding site; RECQL5 interferes with TFIIS-promoted transcriptional read-through in vitro, representing structural mimicry of the Pol II-TFIIS interaction. Cryo-EM structure determination, crystal structure of KIX domain, in vitro transcription read-through assay, binding competition assay Nature structural & molecular biology High 23748380
2013 RECQL5 promotes formation of non-crossover products during DSB-induced HR by acting during the post-synaptic phase of synthesis-dependent strand annealing (SDSA); RECQL5 counteracts the inhibitory effect of RAD51 on RAD52-mediated DNA annealing in vitro; RECQL5 deficiency increases RAD51 occupancy at DSB sites and elevates SCE upon inactivation of the Holliday junction dissolution pathway. HR reporter assay in cells, in vitro annealing assay with purified proteins, ChIP for RAD51 at DSB sites, SCE assay Nucleic acids research High 24319145
2014 RECQL5 depletion causes a genome-wide shift in RNAPII density; loss of RECQL5 increases the average rate of RNAPII elongation concurrent with increased stalling, pausing, arrest, and/or backtracking (transcription stress); chromosomal breakpoints in RECQL5-depleted cells overlap with areas of elevated transcription stress. Genome-wide RNAPII ChIP-seq, chromosomal copy-number analysis, RNA-seq Cell High 24836610
2015 RECQL5 promotes SUMOylation of TOP1 at K391 and K436 by facilitating interaction between the PIAS1-SRSF1 E3 ligase complex and TOP1 in chromatin containing active RNAPII; this SUMOylation is necessary for TOP1 binding to RNAPIIo, recruitment of RNA splicing factors to transcribed chromatin, and reduction of R-loops; SUMOylation also negatively regulates TOP1 topoisomerase activity. In vivo SUMOylation assays, co-immunoprecipitation, ChIP, R-loop detection (S9.6 antibody), mutagenesis of SUMOylation sites Nature communications High 25851487
2016 RECQL5 associates with both RNAPI and RNAPII transcription complexes in DNA replication foci; RECQL5 counteracts replication fork stalling in RNAPI- and RNAPII-transcribed genes; RECQL5-deficient cells accumulate RAD18 foci and BRCA1-dependent RAD51 foci at sites of replication-transcription interference; RECQL5-PCNA interaction promotes RAD18-dependent PCNA ubiquitination and helicase activity promotes processing of replication intermediates. Co-immunoprecipitation, immunofluorescence, DNA fiber assay, PCNA ubiquitination assay, RECQL5-PCNA interaction domain mapping The Journal of cell biology High 27502483
2017 RECQL5 associates with common fragile sites (CFSs) in early mitosis through physical interaction with MUS81, dependent on CDK1-mediated phosphorylation at Ser727; RECQL5 promotes MUS81-dependent mitotic DNA synthesis; RECQL5 alleviates the inhibitory effect of RAD51 on 3'-flap DNA cleavage by MUS81-EME1 through its RAD51 filament disruption activity; mutation of Ser727 or the RAD51-interacting domain impairs CFS expression and causes defective chromosome segregation. Co-immunoprecipitation, ChIP at CFS loci, DNA synthesis assay, in vitro cleavage assay with purified proteins, CDK1 phosphorylation assay, phosphorylation-site mutant analysis Molecular cell High 28575661
2017 Crystal structures of the RECQL5 core helicase domain in 'Open' and 'Closed' conformations (with and without ADP) reveal the mechano-chemical cycle; SAXS shows the 'Open' form predominates in solution; structure-guided mutagenesis defines residues important for ATPase, helicase, and DNA binding activities. X-ray crystallography, small-angle X-ray scattering (SAXS), ATPase assay, helicase assay, mutagenesis Nucleic acids research High 28100692
2021 Single-molecule imaging shows RECQL5 is an ATP-dependent ssDNA motor protein that translocates on RPA-coated ssDNA and on RAD51-coated ssDNA, readily dismantling RAD51-ssDNA filaments; disruption of the RECQL5-RAD51 protein-protein interface (F666A mutation) reduces translocation velocity ~50%; RECQL5 can remove ATP-hydrolysis-deficient RAD51-K133R and the enhanced-binding RAD51-I287T mutant from ssDNA; RECQL5 cannot dismantle RAD51-bound heteroduplex joint molecules. Single-molecule TIRF imaging, ensemble kinetic assays, purified protein reconstitution, RECQL5-F666A mutant analysis Nucleic acids research High 33332547
2021 ATRX-dependent HR outcompetes RECQL5-dependent SDSA for repair of most two-ended DSBs; subpathway choice depends on interaction of both ATRX and RECQL5 with PCNA; RECQL5-dependent SDSA prevents CO formation as assessed by SCE measurements. HR subpathway reporter assays, SCE assay, PCNA interaction domain analysis, genetic epistasis with ATRX/RECQL5/MUS81/GEN1 knockouts Proceedings of the National Academy of Sciences of the United States of America High 33431668
2012 Both the helicase and KIX domains of RECQL5 are required for its recruitment to DSBs; the MRN complex recruits RECQL5 to DSBs independently of its exonuclease activity; RECQL5 recruitment is also independent of transcription by RNAPII, of BLM, WRN, and ATM. Live cell confocal imaging with domain deletion mutants, laser-induced DSB recruitment assay, co-depletion experiments DNA repair Medium 22633600
2012 RECQL5 interacts physically and functionally with WRN helicase; RECQL5 co-operates with WRN on stalled replication fork-like structures and stimulates WRN helicase activity on DNA fork duplexes; both proteins re-localize from nucleolus to nucleus after replicative stress; RECQL5 is essential for cell survival in the absence of WRN (synthetic lethality). Co-immunoprecipitation, in vitro helicase stimulation assay, immunofluorescence co-localization, double knockout cell viability assay Nucleic acids research High 23180761 28180303
2012 RECQL5 depletion causes sensitivity to oxidative stress, accumulation of endogenous DNA damage, increased poly(ADP-ribosyl)ation response, and accumulation at laser-induced single-strand breaks (not DSBs); RECQL5 depletion affects PARP-1 and XRCC1 protein levels, suggesting RECQL5 participates in base excision repair. Laser microirradiation (SSB vs DSB), comet assay, immunofluorescence, western blot for PARP-1 and XRCC1, siRNA knockdown Molecular biology of the cell Medium 22973052
2010 RECQL5 is identified within a super complex containing SWI/SNF chromatin remodeling complex and RNAPII core complex; RECQL5 is detected in the RNAPII holoenzyme but not purified RNAPII core complex. Biochemical purification of complex, co-immunoprecipitation, mass spectrometry International journal of biochemistry and molecular biology Medium 21968968
2015 PARP1 and PAR (poly(ADP-ribose)) regulate RECQL5 activity and recruitment to laser-induced DNA damage; PARylation is involved in recruitment of RECQL5 to damage sites; RECQL5 interacts noncovalently with PAR; PARP inhibition causes increased sensitivity in RECQL5-depleted cells. Laser microirradiation recruitment assay, in vitro PAR-binding assay, co-immunoprecipitation with PARP1, PARP inhibitor sensitivity assay Molecular and cellular biology Medium 26391948
2015 RECQL5 possesses relatively strong strand annealing activity on long and short duplexed substrates compared to other RecQ helicases; unlike other RecQs, its annealing activity is not inhibited by ATP; RECQL5 efficiently catalyzes RNA-to-DNA annealing in vitro in presence or absence of ATP. In vitro strand annealing assays with purified proteins, comparison across all five human RecQ helicases, ATP titration DNA repair Medium 26717024
2016 RECQL5 can unfold G-quadruplex (GQ) DNA structures in a single-molecule assay, but with ~10-fold weaker activity than BLM and WRN; RECQL5 demonstrates ssDNA reeling activity comparable to BLM; GQ unfolding and ssDNA reeling activities are not coupled for RECQL5. Single-molecule FRET imaging, multiple GQ substrates, ATP concentration titration Biophysical journal Medium 27332117
2020 An alternative splicing isoform of RECQL5 (RECQL5β1) containing 17 extra amino acids in the KIX domain has markedly decreased binding affinity to RNAPII, weaker transcription elongation repression activity, but stronger binding to MRE11 and enhanced DSB repair activity compared to canonical RECQL5β. Isoform identification, binding affinity assay, in vitro transcription assay, co-immunoprecipitation with MRE11, DNA repair assay in rescue cells DNA repair Medium 33197722
2025 Cryo-EM structures of stalled human Pol II elongation complexes bound to RECQL5 reveal that RECQL5 contacts the Rpb1 jaw domain acting as a transcriptional roadblock; in its nucleotide-free state RECQL5 twists the downstream DNA in the elongation complex; upon nucleotide binding, RECQL5 undergoes a conformational change that allosterically induces Pol II toward a post-translocation state. Cryo-electron microscopy structure determination of Pol II EC-RECQL5 complexes, in vitro transcription assays Nature structural & molecular biology High 40624164
2025 Cryo-EM structures of RECQL5 bound to multiple Pol II elongation complexes reveal an α-helix of RECQL5 ('brake helix') responsible for binding Pol II and slowing transcription elongation; the transcription-coupled DNA repair (TCR) complex allows Pol II to overcome RECQL5-induced braking through concerted translocase activity and competition with RECQL5 for Pol II engagement; RECQL5 inhibits TCR-mediated Pol II ubiquitination to prevent activation of DNA repair pathway. Cryo-EM structure determination, biochemical transcription elongation assay, RECQL5 deletion/mutation analysis, TCR complex competition assay, Pol II ubiquitination assay Nature structural & molecular biology High 40624163
2025 RECQL5 localizes to the dense fibrillar component of the nucleolus, associates with pre-rRNA processing factors, recognizes pre-rRNA, and can unwind double-stranded RNA in vitro; loss of RECQL5 causes accumulation of 47S, 30SL5', and 30S pre-rRNA and reduction of 21S pre-rRNA, indicating a role in pre-rRNA processing; loss of RECQL5 causes unprocessed pre-rRNA to hybridize with rDNA, triggering R-loop formation and ATR activation. Immunofluorescence/co-localization, co-immunoprecipitation with pre-rRNA processing factors, in vitro dsRNA unwinding assay, Northern blot for pre-rRNA intermediates, R-loop detection (S9.6), ATR activation assay Nucleic acids research High 40823811
2025 RECQL5 localizes to stalled replication fork sites and restricts RAD51-mediated excessive fork reversal to promote unrestrained DNA synthesis; this function requires RECQL5 binding to PCNA, RAD51, and helicase activity but is independent of its RNAPII interaction; notably, the RECQL5 mutant lacking RAD51 interaction still regulates transcription elongation comparably to wild-type, demonstrating that fork reversal regulation and transcription elongation regulation are molecularly distinct functions. DNA fiber assay, proximity ligation assay at forks, co-depletion epistasis with SMARCAL1/ZRANB3/HLTF/FBH1, HR-defective RAD51 mutant rescue, PCNA-interaction and RNAPII-interaction domain mutants Nucleic acids research High 41099703
2025 RECQL5 uses a 'brake helix' as a doorstop to control RNAPII translocation along DNA at the atomic level; at the mesoscale level RECQL5 forms a condensate scaffold matrix integrating phosphorylated RNAPII elongation complex through site-specific interactions. Cryo-EM, cryo-electron tomography, coarse-grained molecular simulations, biochemical reconstitution bioRxivpreprint Medium bio_10.1101_2025.02.05.636647
2024 IWS1 protects the activated transcription elongation complex from RECQL5 inhibition by binding the RPB1 jaw domain competitively with RECQL5, both of which share this binding site. Cryo-EM structure of elongation complexes, binding competition assay, functional transcription assay bioRxivpreprint Medium bio_10.1101_2025.08.28.672863
2008 Deletion of Recql5 in mice results in cancer susceptibility; Recql5-deficient cells exhibit elevated frequencies of spontaneous DNA double-strand breaks and HR events, and are prone to gross chromosomal rearrangements under replication stress. Mouse knockout, tumor incidence analysis, HR reporter assay, chromosomal rearrangement assay Genes & development High 18003859

Source papers

Stage 0 corpus · 83 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2007 RECQL5/Recql5 helicase regulates homologous recombination and suppresses tumor formation via disruption of Rad51 presynaptic filaments. Genes & development 290 18003859
2014 RECQL5 controls transcript elongation and suppresses genome instability associated with transcription stress. Cell 162 24836610
2008 A RECQ5-RNA polymerase II association identified by targeted proteomic analysis of human chromatin. Proceedings of the National Academy of Sciences of the United States of America 124 18562274
2000 Human RecQ5beta, a large isomer of RecQ5 DNA helicase, localizes in the nucleoplasm and interacts with topoisomerases 3alpha and 3beta. Nucleic acids research 124 10710432
2005 Recql5 and Blm RecQ DNA helicases have nonredundant roles in suppressing crossovers. Molecular and cellular biology 110 15831450
2017 RECQ5 Helicase Cooperates with MUS81 Endonuclease in Processing Stalled Replication Forks at Common Fragile Sites during Mitosis. Molecular cell 91 28575661
2010 Physical interaction of RECQ5 helicase with RAD51 facilitates its anti-recombinase activity. The Journal of biological chemistry 83 20348101
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
2016 RECQ5 helicase promotes resolution of conflicts between replication and transcription in human cells. The Journal of cell biology 71 27502483
2010 RECQ5 helicase associates with the C-terminal repeat domain of RNA polymerase II during productive elongation phase of transcription. Nucleic acids research 65 20705653
2010 RecQL5 promotes genome stabilization through two parallel mechanisms--interacting with RNA polymerase II and acting as a helicase. Molecular and cellular biology 64 20231364
2009 Direct inhibition of RNA polymerase II transcription by RECQL5. The Journal of biological chemistry 57 19570979
1999 Drosophila and human RecQ5 exist in different isoforms generated by alternative splicing. Nucleic acids research 54 10471747
2008 Recql5 plays an important role in DNA replication and cell survival after camptothecin treatment. Molecular biology of the cell 53 18987339
2015 RECQ5-dependent SUMOylation of DNA topoisomerase I prevents transcription-associated genome instability. Nature communications 51 25851487
2013 Human RECQ5 helicase promotes repair of DNA double-strand breaks by synthesis-dependent strand annealing. Nucleic acids research 48 24319145
2009 MRE11 complex links RECQ5 helicase to sites of DNA damage. Nucleic acids research 47 19270065
2011 The SET2-RPB1 interaction domain of human RECQ5 is important for transcription-associated genome stability. Molecular and cellular biology 45 21402780
2003 Analysis of helicase activity and substrate specificity of Drosophila RECQ5. Nucleic acids research 41 12595564
2011 RECQL5 cooperates with Topoisomerase II alpha in DNA decatenation and cell cycle progression. Nucleic acids research 40 22013166
2012 A variant of the breast cancer type 2 susceptibility protein (BRC) repeat is essential for the RECQL5 helicase to interact with RAD51 recombinase for genome stabilization. The Journal of biological chemistry 37 22645136
2013 Structural mimicry in transcription regulation of human RNA polymerase II by the DNA helicase RECQL5. Nature structural & molecular biology 34 23748380
2016 A Comparative Study of G-Quadruplex Unfolding and DNA Reeling Activities of Human RECQ5 Helicase. Biophysical journal 31 27332117
2014 RECQL5 and BLM exhibit divergent functions in cells defective for the Fanconi anemia pathway. Nucleic acids research 31 25520194
2012 Recruitment and retention dynamics of RECQL5 at DNA double strand break sites. DNA repair 31 22633600
2017 Insights into the RecQ helicase mechanism revealed by the structure of the helicase domain of human RECQL5. Nucleic acids research 28 28100692
2021 ATRX and RECQ5 define distinct homologous recombination subpathways. Proceedings of the National Academy of Sciences of the United States of America 27 33431668
2015 RECQL5 Suppresses Oncogenic JAK2-Induced Replication Stress and Genomic Instability. Cell reports 27 26686625
2013 Human RECQL5: guarding the crossroads of DNA replication and transcription and providing backup capability. Critical reviews in biochemistry and molecular biology 27 23627586
2013 Association of RECQL5 gene polymorphisms and osteosarcoma in a Chinese Han population. Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine 26 24287950
2012 Human RECQL5 participates in the removal of endogenous DNA damage. Molecular biology of the cell 25 22973052
2012 RECQL5 plays co-operative and complementary roles with WRN syndrome helicase. Nucleic acids research 23 23180761
2010 RECQL5 helicase: connections to DNA recombination and RNA polymerase II transcription. DNA repair 23 20080450
2003 Deficiency of Caenorhabditis elegans RecQ5 homologue reduces life span and increases sensitivity to ionizing radiation. DNA repair 23 14642561
2020 RECQ5: A Mysterious Helicase at the Interface of DNA Replication and Transcription. Genes 22 32098287
2014 Association between RECQL5 genetic polymorphisms and susceptibility to breast cancer. Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine 22 25394896
2021 Targeting RECQL5 Functions, by a Small Molecule, Selectively Kills Breast Cancer in Vitro and in Vivo. Journal of medicinal chemistry 21 33529023
2021 Single-molecule visualization of human RECQ5 interactions with single-stranded DNA recombination intermediates. Nucleic acids research 20 33332547
2008 Loss of RecQ5 leads to spontaneous mitotic defects and chromosomal aberrations in Drosophila melanogaster. DNA repair 20 19013260
2016 Altered RECQL5 expression in urothelial bladder carcinoma increases cellular proliferation and makes RECQL5 helicase activity a novel target for chemotherapy. Oncotarget 19 27764811
2015 Decreased RECQL5 correlated with disease progression of osteosarcoma. Biochemical and biophysical research communications 19 26499077
2001 Biochemical characterization of the small isoform of Drosophila melanogaster RECQ5 helicase. Nucleic acids research 19 11452023
2020 RECQL5 at the Intersection of Replication and Transcription. Frontiers in cell and developmental biology 18 32523948
2019 RECQL5: Another DNA helicase potentially involved in hereditary breast cancer susceptibility. Human mutation 18 30817846
2019 RECQL5 plays an essential role in maintaining genome stability and viability of triple-negative breast cancer cells. Cancer medicine 17 31231988
2010 Human RECQL5 overcomes thymidine-induced replication stress. DNA repair 17 20643585
2015 Differential and Concordant Roles for Poly(ADP-Ribose) Polymerase 1 and Poly(ADP-Ribose) in Regulating WRN and RECQL5 Activities. Molecular and cellular biology 15 26391948
2015 Single nucleotide polymorphism in the RECQL5 gene increased osteosarcoma susceptibility in a Chinese Han population. Genetics and molecular research : GMR 13 25867335
2015 RECQL5 has unique strand annealing properties relative to the other human RecQ helicase proteins. DNA repair 13 26717024
2011 Anaphase DNA bridges induced by lack of RecQ5 in Drosophila syncytial embryos. FEBS letters 13 21570978
2002 Drosophila melanogaster RECQ5/QE DNA helicase: stimulation by GTP binding. Nucleic acids research 13 12202752
2020 Human RECQL5 promotes metastasis and resistance to cisplatin in non-small cell lung cancer. Life sciences 12 33217443
2018 Increased levels of RECQ5 shift DNA repair from canonical to alternative pathways. Nucleic acids research 12 30107528
2013 The RecQ helicase RECQL5 participates in psoralen-induced interstrand cross-link repair. Carcinogenesis 12 23715498
2010 Effect of Recql5 deficiency on the intestinal tumor susceptibility of Apc(min) mice. World journal of gastroenterology 12 20333788
2013 Haplotype analysis of RECQL5 gene and laryngeal cancer. Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine 11 24213927
2011 A Blm-Recql5 partnership in replication stress response. Journal of molecular cell biology 11 21278449
2010 Drosophila RecQ5 is required for efficient SSA repair and suppression of LOH in vivo. Protein & cell 11 21203963
2007 Analyses of functional interaction between RECQL1, RECQL5, and BLM which physically interact with DNA topoisomerase IIIalpha. Biochimica et biophysica acta 11 18078829
2016 Exome Sequencing in a Family Identifies RECQL5 Mutation Resulting in Early Myocardial Infarction. Medicine 10 26844521
2014 Tumor suppressor RecQL5 controls recombination induced by DNA crosslinking agents. Biochimica et biophysica acta 10 24418621
2011 RECQL5 is an important determinant for camptothecin tolerance in human colorectal cancer cells. Bioscience reports 9 21210765
2004 The possible roles of the DNA helicase and C-terminal domains in RECQ5/QE: complementation study in yeast. DNA repair 9 15010312
2025 Structural insights into transcriptional regulation by the helicase RECQL5. Nature structural & molecular biology 8 40624164
2015 Recql5 protects against lipopolysaccharide/D-galactosamine-induced liver injury in mice. World journal of gastroenterology 8 26420964
2025 Structural basis of RECQL5-induced RNA polymerase II transcription braking and subsequent reactivation. Nature structural & molecular biology 7 40624163
2012 RecQ5 interacts with Rad51 and is involved in resistance of Drosophila to cisplatin treatment. Biological & pharmaceutical bulletin 7 23123473
2010 Purification of a novel RECQL5-SWI/SNF-RNAPII super complex. International journal of biochemistry and molecular biology 7 21968968
2023 Functional inhibition of RECQL5 helicase elicits non-homologous end joining response and sensitivity of breast cancers to PARP inhibitor. The international journal of biochemistry & cell biology 6 37392863
2017 RECQL5 plays co-operative and complementary roles with WRN syndrome helicase. Nucleic acids research 6 28180303
2006 Relationships of Drosophila melanogaster RECQ5/QE to cell-cycle progression and DNA damage. FEBS letters 6 17157839
2022 A Large Case-Control Study Performed in Spanish Population Suggests That RECQL5 Is the Only RECQ Helicase Involved in Breast Cancer Susceptibility. Cancers 5 36230663
2025 Distinct roles of RECQL5 in RAD51-mediated fork reversal and transcription elongation. Nucleic acids research 4 41099703
2025 RECQ5 mediates pre-rRNA processing in nucleolus. Nucleic acids research 3 40823811
2023 Understanding the Human RECQ5 Helicase-Connecting the Dots from DNA to Clinics. Cells 3 37626846
2013 RecQ5 protein translocation into the nucleus by a nuclear localization signal. Biological & pharmaceutical bulletin 3 23811565
2025 Structural insights into transcriptional regulation by the helicase RECQL5. bioRxiv : the preprint server for biology 2 39975028
2024 A Recql5 mutant facilitates complex CRISPR/Cas9-mediated chromosomal engineering in mouse zygotes. Genetics 2 38577877
2020 RECQL5 KIX domain splicing isoforms have distinct functions in transcription repression and DNA damage response. DNA repair 2 33197722
2014 Drosophila RecQ5 is involved in proper progression of early spermatogenesis. Biochemical and biophysical research communications 2 25245292
2025 Recql5-Deficient Mice as a Model for Studying Chromoanagenesis Phenomena. Methods in molecular biology (Clifton, N.J.) 0 40884668
2024 Expression of human RECQL5 in Saccharomyces cerevisiae causes transcription defects and transcription-associated genome instability. Molecular genetics and genomics : MGG 0 38796829
2011 [Role of RecQ5 in syncytial blastoderm of the Drosophila embryo]. Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan 0 21963973

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