Affinage

RECQL5

ATP-dependent DNA helicase Q5 · UniProt O94762

Length
991 aa
Mass
108.9 kDa
Annotated
2026-04-28
83 papers in source corpus 35 papers cited in narrative 36 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

RECQL5 is a RecQ-family DNA helicase that serves as a dual-function genome stability factor, operating both as a regulator of homologous recombination and as a transcription elongation modulator for RNA polymerase II. In its recombination role, RECQL5 acts as an ATP-dependent ssDNA translocase that disrupts RAD51 presynaptic filaments via a BRC repeat variant and a mapped RAD51-interaction domain, channeling double-strand break repair toward synthesis-dependent strand annealing and suppressing crossovers; this activity also extends to removing RAD51 from stalled replication forks to restrict excessive fork reversal and to enabling MUS81-dependent mitotic DNA synthesis at common fragile sites through CDK1-phosphorylation-dependent recruitment (PMID:18003859, PMID:22645136, PMID:33332547, PMID:28575661, PMID:41099703). In its transcription role, RECQL5 binds elongating RNAPII through KIX and SRI domains—the latter recognizing the Ser2,5-phosphorylated CTD of RPB1—and acts as a steric brake on elongation, as demonstrated by cryo-EM structures showing its helicase domain blocking the downstream DNA channel and a brake helix controlling translocation; loss of this function causes transcription stress, R-loop accumulation, and replication-transcription collisions that generate DNA breaks at actively transcribed loci and fragile sites (PMID:20705653, PMID:24836610, PMID:40624164, PMID:40624163). RECQL5 additionally promotes TOP1 SUMOylation to facilitate proper co-transcriptional RNA processing and R-loop resolution, stimulates Topoisomerase IIα decatenation activity during S-phase, cooperates with the MRN complex at DSB sites, and processes pre-rRNA in the nucleolus (PMID:25851487, PMID:22013166, PMID:19270065, PMID:40823811).

Mechanistic history

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

    Establishing that the major RECQL5 isoform (RecQ5β) is a nuclear protein with topoisomerase III interactions resolved basic questions about subcellular context and potential functional partnerships for this poorly characterized RecQ helicase.

    Evidence Immunocytochemistry of tagged isoforms in 293EBNA cells; co-IP with topoisomerase 3α/3β

    PMID:10710432

    Open questions at the time
    • Functional significance of Topo3α/3β interaction not tested
    • Overexpression-based localization may not reflect endogenous protein
  2. 2005 High

    Genetic evidence that RECQL5 and BLM non-redundantly suppress sister chromatid exchanges established RECQL5 as a bona fide anti-recombinase acting through a pathway distinct from the BLM dissolution mechanism.

    Evidence SCE measurement in Recql5/Blm single and double knockout mouse ES cells and MEFs

    PMID:15831450

    Open questions at the time
    • Biochemical mechanism of SCE suppression unknown at this point
    • No direct substrate or interaction partner identified
  3. 2007 High

    Demonstration that RECQL5 directly binds RAD51 and dismantles presynaptic filaments in an ATP- and RPA-dependent manner provided the molecular mechanism for its anti-recombinase activity.

    Evidence In vitro reconstitution with purified proteins, EM visualization of filament disruption, D-loop assays, mouse knockout HR reporter

    PMID:18003859

    Open questions at the time
    • Structural basis of RAD51 interaction not yet mapped
    • Whether RECQL5 acts as a translocase on ssDNA or uses a different mechanism was unknown
  4. 2008 High

    Discovery that RECQL5 is the only human RecQ helicase that directly associates with RNAPII revealed an unexpected second functional axis—transcription regulation—distinct from its recombination role.

    Evidence Targeted proteomics of chromatin-associated factors; direct interaction reconstituted with purified RECQL5 and RPB1

    PMID:18562274

    Open questions at the time
    • Domain mediating Pol II interaction not yet mapped
    • Functional consequence of the interaction unknown
  5. 2009 High

    Two parallel discoveries defined RECQL5's interactions at DNA damage sites: it constitutively associates with the MRN complex (inhibiting MRE11 exonuclease) and it directly inhibits RNAPII transcription initiation and elongation independent of helicase activity.

    Evidence Co-IP with MRN components, in vitro exonuclease inhibition, laser-induced DSB recruitment (PMID:19270065); reconstituted in vitro transcription with purified GTFs and RNAPII, helicase-dead mutant (PMID:19570979)

    PMID:19270065 PMID:19570979

    Open questions at the time
    • Structural basis of MRN interaction not determined
    • How helicase-independent transcription inhibition is achieved mechanistically was unclear
  6. 2010 High

    Mapping of the SRI and KIX domains as dual RNAPII-binding modules, and the RAD51-interaction domain as the anti-recombinase interface, established the modular domain architecture underlying RECQL5's bifunctional activities.

    Evidence SRI domain binding to Ser2,5-phospho CTD by ChIP and in vitro binding (PMID:20705653); KIX domain binding Pol IIa/IIo with mutagenesis and SCE assays (PMID:20231364); RAD51-interaction domain point mutants disrupting filament displacement (PMID:20348101)

    PMID:20231364 PMID:20348101 PMID:20705653

    Open questions at the time
    • Atomic-resolution structures of these domain–partner complexes not yet available
    • How KIX and SRI domains coordinate during transcription elongation not resolved
  7. 2011 High

    Connecting RECQL5's SRI-mediated RNAPII association to genome stability showed that loss of RECQL5 causes RNAPII-dependent double-strand breaks, establishing transcription stress as the proximal cause of genomic instability in RECQL5-deficient cells.

    Evidence SRI domain mutants, ChIP for active RNAPII, γH2AX/DSB assays rescued by transcription inhibitors

    PMID:21402780

    Open questions at the time
    • Genomic locations of transcription-dependent breaks not mapped
    • Whether R-loops mediate the breaks was not tested
  8. 2011 High

    Discovery that RECQL5 physically stimulates Topoisomerase IIα decatenation activity expanded its functional repertoire beyond recombination and transcription to chromosome topology maintenance during S-phase.

    Evidence Co-IP, in vitro decatenation stimulation assay, co-localization in S-phase, chromosome entanglement phenotype upon RECQL5 depletion

    PMID:22013166

    Open questions at the time
    • Mechanism of stimulation (conformational change vs. recruitment) not determined
    • Whether this is independent of RECQL5 helicase activity not tested
  9. 2012 High

    Identification of a BRC repeat variant in RECQL5 that mimics BRCA2's RAD51-binding motifs provided the structural rationale for how RECQL5 engages the RAD51 protomer to disrupt filaments, while WRN interaction studies and DSB recruitment mapping further contextualized RECQL5's role at replication and damage sites.

    Evidence BRCv motif mutagenesis with D-loop, SCE, and binding assays (PMID:22645136); WRN co-IP and helicase stimulation assay, synthetic lethality (PMID:23180761); domain deletion live imaging at laser DSBs (PMID:22633600)

    PMID:22633600 PMID:22645136 PMID:23180761

    Open questions at the time
    • Crystal structure of BRCv-RAD51 interface not solved
    • Whether WRN stimulation is direct or mediated through substrate remodeling unclear
  10. 2013 High

    The first cryo-EM structure of RECQL5 bound to elongating Pol II revealed that its helicase domain sterically blocks the downstream DNA channel while its KIX domain competes with TFIIS, providing the atomic-level explanation for transcription inhibition and crossover suppression via non-crossover HR channeling.

    Evidence Cryo-EM of Pol II–RECQL5, KIX crystal structure, TFIIS competition assay (PMID:23748380); in vitro strand annealing showing RECQL5 counteracts RAD51 inhibition of RAD52-mediated annealing (PMID:24319145)

    PMID:23748380 PMID:24319145

    Open questions at the time
    • Resolution insufficient to define brake helix contacts
    • How RECQL5 switches between transcription-inhibitory and HR-regulatory modes not addressed
  11. 2014 High

    Genome-wide RNAPII profiling upon RECQL5 depletion demonstrated that RECQL5 acts as a global transcription elongation rate regulator, with its loss causing increased elongation speed coupled with elevated stalling, and chromosomal breaks mapping to actively transcribed genes and fragile sites.

    Evidence Genome-wide RNAPII ChIP-seq, copy number analysis, RECQL5 depletion and overexpression showing reciprocal effects

    PMID:24836610

    Open questions at the time
    • Direct mechanism linking faster elongation to increased stalling not resolved
    • Whether RECQL5 acts at all genes or a subset preferentially was not fully distinguished
  12. 2015 High

    Discovery that RECQL5 promotes TOP1 SUMOylation via the PIAS1-SRSF1 complex, enabling TOP1 to associate with active RNAPII and reduce R-loops, connected RECQL5's transcription role to co-transcriptional RNA processing and topological stress management.

    Evidence SUMOylation assays, K391/K436 mutagenesis, R-loop measurement, topoisomerase activity assays, chromatin fractionation

    PMID:25851487

    Open questions at the time
    • Whether RECQL5's helicase activity contributes to this function not tested
    • How RECQL5 facilitates PIAS1-TOP1 interaction structurally is unknown
  13. 2016 High

    Establishing that RECQL5 operates at replication-transcription collision sites—associating with both RNAPI/RNAPII complexes in replication foci and promoting PCNA ubiquitination—linked its transcription and replication functions mechanistically.

    Evidence Co-IP, PLA, ChIP, PCNA ubiquitination assay, DNA fiber analysis in RECQL5-depleted cells

    PMID:27502483

    Open questions at the time
    • Direct structural basis of PCNA interaction not mapped
    • Whether PCNA ubiquitination function is separable from RAD51 displacement not tested
  14. 2017 High

    Demonstration that CDK1-phosphorylated RECQL5 associates with common fragile sites in early mitosis to remove RAD51 filaments and enable MUS81-dependent mitotic DNA synthesis explained how RECQL5 prevents under-replicated DNA from causing mitotic errors, while crystal structures of the helicase core in open/closed conformations defined the mechanochemical cycle.

    Evidence ChIP at CFSs, S727A phosphomutant, in vitro 3′-flap cleavage with RAD51 ± RECQL5 (PMID:28575661); X-ray crystallography, SAXS, ATPase/helicase assays (PMID:28100692)

    PMID:28100692 PMID:28575661

    Open questions at the time
    • Whether phosphorylation at S727 affects other RECQL5 interactions not examined
    • Structure of full-length RECQL5 including KIX/SRI domains not determined
  15. 2021 High

    Single-molecule imaging revealed RECQL5 as an ATP-dependent ssDNA translocase that dismantles RAD51 filaments through motor activity on the DNA lattice, while genetic epistasis established that RECQL5-dependent SDSA and ATRX-dependent HR represent competing DSB repair pathways governed by PCNA interaction.

    Evidence Single-molecule TIRF microscopy with RECQL5-F666A and RAD51-K133R mutants (PMID:33332547); epistasis with ATRX/BLM/MUS81/GEN1 knockouts and PCNA mutants (PMID:33431668)

    PMID:33332547 PMID:33431668

    Open questions at the time
    • How PCNA interaction governs pathway choice mechanistically is unclear
    • Whether RECQL5 translocase activity contributes to transcription regulation not tested
  16. 2025 High

    High-resolution cryo-EM structures of RECQL5 on stalled Pol II elongation complexes identified the brake helix as the key structural element controlling translocation, showed nucleotide-dependent conformational switching that can restart paused Pol II, and revealed that the TCR complex competes with RECQL5 for Pol II engagement; separately, RECQL5 was shown to restrict RAD51-mediated fork reversal independently of its RNAPII interaction, and to function in pre-rRNA processing in the nucleolus.

    Evidence Cryo-EM in nucleotide-free and bound states (PMID:40624164, PMID:40624163); DNA fiber assays with fork remodeler co-depletions and domain-separation mutants (PMID:41099703); nucleolar localization, dsRNA unwinding, Northern blots for pre-rRNA (PMID:40823811)

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

    Open questions at the time
    • Full-length RECQL5 structure including all regulatory domains on Pol II not yet resolved
    • Mechanism of nucleolar pre-rRNA processing function requires reconstitution
    • Whether condensate formation is physiologically relevant awaits in vivo validation

Open questions

Synthesis pass · forward-looking unresolved questions
  • Major unresolved questions include: how RECQL5 switches between its separable transcription-regulatory and recombination/replication functions in vivo; the structural basis of RECQL5 engagement with PCNA, MRN, and Topo IIα; and whether RECQL5's nucleolar rRNA processing role is mechanistically linked to its genome maintenance functions.
  • No in vivo structural data for full-length RECQL5 in complex with any partner
  • Regulation of RECQL5 by post-translational modifications beyond S727 phosphorylation largely unexplored
  • Pathological consequences of RECQL5 loss in human disease not established through genetic studies

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0008092 cytoskeletal protein binding 4 GO:0098772 molecular function regulator activity 4 GO:0003677 DNA binding 3 GO:0140657 ATP-dependent activity 3 GO:0140096 catalytic activity, acting on a protein 2 GO:0003723 RNA binding 1 GO:0140098 catalytic activity, acting on RNA 1
Localization
GO:0005694 chromosome 3 GO:0005654 nucleoplasm 2 GO:0005730 nucleolus 2
Pathway
R-HSA-74160 Gene expression (Transcription) 8 R-HSA-73894 DNA Repair 6 R-HSA-69306 DNA Replication 3 R-HSA-1640170 Cell Cycle 2 R-HSA-8953854 Metabolism of RNA 1
Partners
MRE11MUS81NBS1PCNARAD51RPB1TOP2AWRN
Complex memberships
MRN complex (associated)RNAPII elongation complex

Evidence

Reading pass · 36 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2007 RECQL5 binds the 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, disrupting RAD51 presynaptic filaments to suppress homologous recombination In vitro biochemical assays with purified proteins, electron microscopy, D-loop formation assays, mouse knockout model with HR reporter Genes & development High 18003859
2000 The RecQ5beta isoform (991 aa) localizes exclusively in the nucleoplasm and interacts with topoisomerases 3alpha and 3beta, but not topoisomerase 1; the shorter alpha and gamma isoforms remain cytoplasmic Immunocytochemical staining of tagged isoforms expressed in 293EBNA cells; immunoprecipitation Nucleic acids research Medium 10710432
2008 RECQL5 (RECQ5) is a bona fide RNAPII-associated protein; the interaction is direct and mediated by the RPB1 subunit of RNAPII, and RECQ5 is the only human RECQ family member that associates with RNAPII Targeted proteomic analysis of chromatin-associated factors; direct interaction demonstrated by pulldown with purified proteins Proceedings of the National Academy of Sciences of the United States of America High 18562274
2005 Recql5 and Blm have nonredundant roles in suppressing sister chromatid exchanges (crossovers) during mitosis; deletion of both genes causes additive increases in SCE frequency beyond either single knockout Genetic epistasis in mouse ES cells and MEFs; sister chromatid exchange frequency measurement in single and double knockouts Molecular and cellular biology High 15831450
2009 RECQL5 directly inhibits both initiation and elongation of RNAPII transcription; this inhibition requires the RNAPII-interaction domain of RECQL5 but not its helicase activity In vitro transcription assays reconstituted with highly purified general transcription factors and RNAPII; RNAPII-interaction-defective RECQL5 mutant The Journal of biological chemistry High 19570979
2010 RECQ5 associates with the Ser2,5-phosphorylated CTD of RPB1 via a Set2-Rpb1-interacting (SRI) motif at the RECQ5 C-terminus; RECQ5 associates with RNAPII-transcribed genes in an SRI-dependent manner correlating with productive elongation Co-IP, chromatin immunoprecipitation (ChIP), SRI domain mutation analysis, in vitro binding assays Nucleic acids research High 20705653
2010 RecQL5 interacts with RNAPII through KIX (binds both initiation Pol IIa and elongation Pol IIo forms) and SRI (binds only elongation Pol IIo) domains; both helicase activity and KIX-mediated Pol IIa interaction are required for full genome-stabilizing function Purification of RecQL5-associated complex; bioinformatics/structural modeling-guided mutagenesis; SCE and camptothecin resistance assays Molecular and cellular biology High 20231364
2010 Physical interaction between RECQ5 and RAD51 mapped to a specific RAD51-interacting domain of RECQ5; point mutations abolishing RECQ5-RAD51 complex formation impair RAD51 displacement from ssDNA while retaining normal ATPase activity, and ablation of this interaction alleviates RECQ5 inhibition of HR-mediated DSB repair Domain mapping, point mutagenesis, in vitro RAD51 displacement assays, DSB repair assays in cells The Journal of biological chemistry High 20348101
2009 RECQ5 is constitutively associated with the MRE11-RAD50-NBS1 (MRN) complex through interactions with both MRE11 and NBS1; RECQ5 specifically inhibits the 3'→5' exonuclease activity of MRE11, and the MRN complex is required for recruitment of RECQ5 to sites of DNA damage Co-IP with purified proteins, in vitro exonuclease inhibition assays, laser-induced DSB recruitment assays, cellular epistasis using MRN-depleted cells Nucleic acids research High 19270065
2011 The SRI domain of human RECQ5 is important for suppressing spontaneous DSBs and preventing accumulation of active RNAPII on chromatin; RECQ5 depletion causes RNAPII-dependent DSB formation that is eliminated by transcription inhibition SRI domain mutants, ChIP for active RNAPII, transcription inhibitor treatment, γH2AX/DSB assays in RECQ5-depleted cells Molecular and cellular biology High 21402780
2011 RECQL5 physically interacts with and stimulates the decatenation activity of Topoisomerase IIα; RECQL5 co-localizes with Topo IIα during S-phase, and RECQL5 depletion causes G2/M arrest, undercondensed/entangled chromosomes, and a late S-phase cycling defect phenocopying Topo II inhibition Co-IP, in vitro decatenation stimulation assay, co-localization imaging, cell cycle analysis, metaphase spreads in RECQL5-depleted cells Nucleic acids research High 22013166
2012 RECQL5 contains a BRC repeat variant (BRCv) that mediates RAD51 interaction through two conserved motifs similar to BRCA2-BRC; mutations in either BRCv motif compromise RECQL5 association with RAD51, inhibition of D-loop formation, SCE suppression, and camptothecin resistance Structural/bioinformatics identification, mutagenesis of BRCv motifs, RAD51 binding assays, D-loop assays, SCE measurement, cell survival assays The Journal of biological chemistry High 22645136
2013 RECQL5 contacts the Rpb1 jaw domain of Pol II at a site overlapping with TFIIS binding; cryo-EM structure of elongating Pol II arrested with RECQL5 shows helicase domain positioned to sterically block elongation; RECQL5 KIX domain has structural similarity to TFIIS and competes with TFIIS for Pol II binding to inhibit transcriptional read-through Cryo-EM structure determination, crystal structure of KIX domain, in vitro competition assay with TFIIS, TFIIS read-through assay Nature structural & molecular biology High 23748380
2013 RECQL5 promotes formation of non-crossover products during HR by counteracting the inhibitory effect of RAD51 on RAD52-mediated DNA annealing; RECQL5 deficiency causes increased RAD51 occupancy at DSB sites and elevated SCEs upon inactivation of the Holliday junction dissolution pathway In vitro strand annealing assays with purified proteins, ChIP for RAD51 at DSB sites, SCE measurement in BLM-deficient background, in vivo HR reporter assays Nucleic acids research High 24319145
2014 RECQL5 controls RNAPII elongation genome-wide; depletion causes increased average RNAPII elongation rate with increased stalling/pausing/backtracking (transcription stress), and leads to chromosomal breakpoints at genes and common fragile sites overlapping with regions of elevated transcription stress Genome-wide RNAPII ChIP-seq, RNAPII density profiling, genomic copy number analysis, RECQL5 depletion/overexpression 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; this SUMOylation is required for TOP1 binding to active RNAPII (RNAPIIo) and recruitment of RNA splicing factors, reducing R-loop formation; SUMOylation also negatively regulates TOP1 topoisomerase activity at transcriptionally active chromatin SUMOylation assays, Co-IP, mutagenesis of K391/K436, R-loop measurement, topoisomerase activity assays, chromatin fractionation Nature communications High 25851487
2016 RECQ5 associates with both RNAPI and RNAPII transcription complexes in DNA replication foci; RECQ5 interaction with PCNA promotes RAD18-dependent PCNA ubiquitination; RECQ5 helicase activity promotes processing of replication intermediates at replication-transcription collision sites; RECQ5-deficient cells accumulate RAD18 and BRCA1-dependent RAD51 foci at replication-transcription collision sites Co-IP, proximity ligation assay, ChIP, laser-induced damage recruitment, PCNA ubiquitination assay, DNA fiber analysis in RECQ5-depleted cells The Journal of cell biology High 27502483
2017 RECQ5 associates with common fragile sites (CFSs) during early mitosis via physical interaction with MUS81; CDK1-dependent Ser727 phosphorylation of RECQ5 is required for this association; RECQ5 promotes MUS81-dependent mitotic DNA synthesis at CFSs by removing RAD51 filaments from stalled replication forks, alleviating RAD51 inhibition of MUS81-EME1 3'-flap cleavage activity ChIP at CFSs, Co-IP of RECQ5-MUS81, phosphosite mutagenesis (S727A), in vitro 3'-flap cleavage assays with RAD51 ± RECQ5, DNA fiber analysis, mitotic DNA synthesis assays 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; ATPase, helicase, and DNA binding properties mapped to specific residues and domains X-ray crystallography, SAXS, in vitro ATPase assay, helicase assay, DNA binding assays with domain variants Nucleic acids research High 28100692
2021 RECQ5 acts as an ATP-dependent ssDNA motor protein, translocating on RPA-coated ssDNA and RAD51-coated ssDNA to dismantle RAD51-ssDNA filaments; protein-protein contact between RECQ5 and RAD51 (RECQ5-F666A mutation) reduces translocation velocity ~50% but RECQ5 can still remove ATP hydrolysis-deficient RAD51-K133R; RECQ5 cannot translocate on dsDNA nor dismantle RAD51-bound heteroduplex joint molecules Single-molecule imaging (TIRF microscopy), kinetic assays, RECQ5-F666A and RAD51-K133R mutants, ssDNA and dsDNA substrate specificity assays Nucleic acids research High 33332547
2021 ATRX-dependent HR outcompetes RECQ5-dependent SDSA for repair of most two-ended DSBs; subpathway choice depends on interaction of both ATRX and RECQ5 with PCNA; RECQ5-dependent SDSA prevents crossover formation (SCE) Epistasis analysis with ATRX/RECQ5/BLM/MUS81/GEN1 knockouts, SCE measurement, ultra-fine bridge analysis, PCNA interaction mutants Proceedings of the National Academy of Sciences of the United States of America High 33431668
2012 RECQL5 physically and functionally interacts with WRN helicase; RECQL5 stimulates WRN helicase activity on DNA fork duplexes; both proteins re-localize from nucleolus to nucleus after replication stress and associate during S-phase; loss of both RECQL5 and WRN is synthetically lethal, severely compromising DNA replication Co-IP in vivo and in vitro, helicase stimulation assay, live cell imaging, co-localization, double-knockout cell viability assay Nucleic acids research High 23180761
2012 RECQL5 is recruited early to laser-induced DSBs; both the helicase and KIX domains are required for stable association at DSB sites; recruitment is independent of MDC1, CtIP, BLM, WRN, ATM, RNAPII transcription activity, and MRE11 exonuclease activity, but dependent on MRE11 protein Live cell confocal microscopy with laser-induced DSBs, domain deletion analysis, epistasis with siRNA knockdowns of damage-response factors DNA repair Medium 22633600
2010 RECQL5 purifies within an RNAPII holoenzyme complex containing the SWI/SNF chromatin remodeling complex; RECQL5 is detected in the RNAPII holoenzyme but not purified RNAPII core complex Biochemical purification of RNAPII holoenzyme, mass spectrometry identification International journal of biochemistry and molecular biology Medium 21968968
2015 RECQL5 has distinct strand annealing activity: stronger than other human RecQ helicases on long or short substrates, not inhibited by ATP (unlike other RecQs), and efficiently anneals RNA to DNA in vitro; RPA inhibits while RAD51 stimulates RECQL5 strand annealing In vitro strand annealing assays with purified RECQL5 and all five human RecQ helicases, ATP titration, RNA-DNA annealing, RPA/RAD51/Ku/FEN1 modulation assays DNA repair Medium 26717024
2016 RECQ5 can unfold G-quadruplex (GQ) DNA structures but with ~10-fold weaker activity than BLM and WRN; RECQ5 and BLM have similar ssDNA reeling activities that are not coupled to GQ unfolding Single-molecule FRET/TIRF assays with various GQ constructs under different salt and ATP conditions Biophysical journal Medium 27332117
2015 RECQL5 depletion sensitizes JAK2V617F-mutant cells to hydroxyurea and impairs replication dynamics (assessed by DNA fiber analysis) following HU treatment, resulting in increased DSBs and apoptosis specifically in JAK2V617F cells Single-fiber chromosome combing (DNA fiber analysis), γH2AX/DSB measurement, siRNA depletion of RECQL5 in JAK2V617F vs. wild-type cells Cell reports Medium 26686625
2015 PARP1 and PAR regulate the recruitment and activities of RECQL5; RECQL5 interacts with PAR noncovalently; PARylation is involved in recruitment of RECQL5 to laser-induced DNA damage; RECQL5 loss results in increased sensitivity to PARP inhibition In vitro PAR-binding assays, laser-induced damage recruitment (live imaging), PARP inhibitor sensitivity assays in RECQL5-depleted cells Molecular and cellular biology Medium 26391948
2012 RECQL5 accumulates at laser-induced single-strand breaks (SSBs) and affects levels of PARP-1 and XRCC1; RECQL5 depletion causes sensitivity to oxidative stress and accumulation of endogenous DNA damage, suggesting RECQL5 modulates base excision repair Live cell imaging at laser-induced SSBs, PARP/XRCC1 protein level analysis, oxidative stress sensitivity assays in RECQL5-depleted cells Molecular biology of the cell Medium 22973052
2013 The KIX domain of RECQL5 (amino acids 500–650) mediates recruitment to psoralen-induced interstrand crosslink sites; recruitment is not affected by transcription or topoisomerase inhibition but is inhibited by DNA-intercalating agents, suggesting the DNA structure itself drives recruitment Laser-directed confocal microscopy with ICL induction (trioxalen + UVA), domain deletion mapping with KIX truncation, pharmacological inhibitor analysis Carcinogenesis Medium 23715498
2025 Cryo-EM structures of RECQL5 bound to stalled human Pol II elongation complexes reveal: (1) RECQL5 helicase domain acts as a transcriptional roadblock; (2) in nucleotide-free state, RECQL5 twists downstream DNA in the EC; (3) upon nucleotide binding, RECQL5 undergoes a conformational change that allosterically induces Pol II toward a post-translocation state, potentially restarting elongation Cryo-electron microscopy structure determination of Pol II-RECQL5 elongation complexes in nucleotide-free and nucleotide-bound states Nature structural & molecular biology High 40624164
2025 Cryo-EM structures of RECQL5 bound to Pol II elongation complexes identify an α-helix of RECQL5 (brake helix) responsible for binding Pol II and slowing transcription elongation; the TCR complex allows Pol II to overcome RECQL5-induced braking through translocase activity and competition for Pol II engagement; RECQL5 inhibits TCR-mediated Pol II ubiquitination Cryo-EM structure determination, biochemical transcription elongation assays, TCR complex competition assays, Pol II ubiquitination assays Nature structural & molecular biology High 40624163
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; conversely, RECQL5 regulation of transcription elongation is independent of its RAD51 interaction DNA fiber assays, co-depletion of fork remodelers (SMARCAL1/ZRANB3/HLTF/FBH1), HR-defective RAD51 mutants, PCNA and RNAPII interaction mutants, replication fork reversal assays Nucleic acids research High 41099703
2025 RECQ5 localizes in the dense fibrillar component of the nucleolus, associates with pre-rRNA processing factors, recognizes pre-rRNA and unwinds dsRNA in vitro; loss of RECQ5 causes accumulation of 47S, 30SL5', and 30S pre-rRNA and reduction of 21S pre-rRNA, and triggers R-loop formation on rDNA with ATR activation Immunofluorescence/nucleolar fractionation, Co-IP with pre-rRNA processing factors, in vitro dsRNA unwinding assay, Northern blot for pre-rRNA intermediates, R-loop detection (S9.6 antibody/DRIP), ATR activation assay, cancer variant functional analysis Nucleic acids research Medium 40823811
2020 KIX domain alternative splicing isoform RECQL5β1 (with 17 extra amino acids) has markedly decreased binding affinity to Pol II and weaker transcription repression activity, but binds more strongly to MRE11 and promotes DNA repair at DSBs, demonstrating functional specialization of KIX isoforms Co-IP binding affinity comparison, in vitro transcription repression assays, MRE11 binding assays, DSB repair assays in rescue cell lines expressing each isoform DNA repair Medium 33197722
2025 RECQL5 uses a brake helix as a doorstop to control RNAPII translocation (transcription attenuation at atomic level); at mesoscale, RECQL5 forms a condensate scaffold matrix integrating phosphorylated RNAPII elongation complexes through site-specific interactions, reinforcing condensate structural integrity Biochemical reconstitution, cryo-EM, cryo-electron tomography, coarse-grained molecular simulations bioRxivpreprint Medium

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 289 18003859
2014 RECQL5 controls transcript elongation and suppresses genome instability associated with transcription stress. Cell 160 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 109 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 82 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 69 27502483
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
2010 RECQ5 helicase associates with the C-terminal repeat domain of RNA polymerase II during productive elongation phase of transcription. Nucleic acids research 64 20705653
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 46 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 33 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 16 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
2015 Recql5 protects against lipopolysaccharide/D-galactosamine-induced liver injury in mice. World journal of gastroenterology 8 26420964
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
2025 Structural insights into transcriptional regulation by the helicase RECQL5. Nature structural & molecular biology 5 40624164
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 Structural basis of RECQL5-induced RNA polymerase II transcription braking and subsequent reactivation. Nature structural & molecular biology 4 40624163
2025 Structural insights into transcriptional regulation by the helicase RECQL5. bioRxiv : the preprint server for biology 3 39975028
2025 Distinct roles of RECQL5 in RAD51-mediated fork reversal and transcription elongation. Nucleic acids research 3 41099703
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
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 RECQ5 mediates pre-rRNA processing in nucleolus. Nucleic acids research 1 40823811
2024 A Recql5 mutant facilitates complex CRISPR/Cas9-mediated chromosomal engineering in mouse zygotes. Genetics 1 38577877
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
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