Affinage

BLM

RecQ-like DNA helicase BLM · UniProt P54132

Length
1417 aa
Mass
159.0 kDa
Annotated
2026-04-28
100 papers in source corpus 54 papers cited in narrative 55 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

BLM is an ATP-dependent 3′→5′ RecQ family DNA helicase that functions as the catalytic core of the BTR dissolvasome (BLM–Topoisomerase IIIα–RMI1/BLAP75) to dissolve double Holliday junctions into non-crossover products, thereby suppressing excessive homologous recombination and sister chromatid exchanges (PMID:16595695, PMID:10880455). Operating as a monomer with ~70–80 bp/s processivity, BLM unwinds diverse substrates including replication forks, G-quadruplexes, R-loops, and telomeric D-loops, with its activity modulated by RPA (which enables reinitiation and bidirectional unwinding at nicks), POT1/TRF2 (at telomeres), and CtIP/DNA2 (during long-range end resection), while RAD51 filaments on DNA block BLM translocation, establishing its anti-recombinase function (PMID:19165145, PMID:32101168, PMID:16030011, PMID:29020620, PMID:31544923, PMID:28912125). BLM protein levels and activity are tightly cell-cycle-regulated through MIB1-mediated ubiquitination (promoting G1 degradation), TopBP1-dependent stabilization in S phase via phospho-Ser304 recognition, USP37-mediated deubiquitination enhanced by ATM, and AARS1-catalyzed lactylation at Lys24, while phosphorylation by ATM (Thr99), MPS1 (Ser144/PLK1 docking), CDK, and ATR/Chk1 directs BLM to stalled replication forks, DSBs, meiotic synaptonemal complexes, and anaphase ultrafine bridges for sister chromatid decatenation and centromere integrity maintenance (PMID:24239288, PMID:28919440, PMID:34606619, PMID:40634292, PMID:12034743, PMID:16864798, PMID:17599064, PMID:31253795). BLM additionally participates in rDNA transcription by unwinding GC-rich impediments ahead of RNA Pol I, resolves telomeric R-loops in ALT cells in coordination with FANCM and SLX4IP, and cooperates with p53 at stalled replication forks to regulate recombination and apoptosis (PMID:22106380, PMID:31138795, PMID:31447390, PMID:12606585).

Mechanistic history

Synthesis pass · year-by-year structured walk · 21 steps
  1. 1997 High

    Establishing how BLM reaches the nucleus: identification of its C-terminal bipartite NLS (residues 1334–1349) resolved how this large helicase achieves nuclear targeting.

    Evidence EGFP-fusion deletion constructs expressed in HeLa cells with immunofluorescence

    PMID:9388480

    Open questions at the time
    • Whether NLS is regulated by post-translational modification
    • Mechanism of BLM export or redistribution to cytoplasmic stress granules
  2. 1999 Medium

    Placing BLM in meiotic recombination: BLM localizes to synaptonemal complexes in late zygonema, temporally following RPA, suggesting a role in processing meiotic recombination intermediates.

    Evidence Immunofluorescence of mouse spermatocyte meiotic spreads with SC and RPA co-staining

    PMID:10318934

    Open questions at the time
    • No functional loss-of-function meiotic data in this study
    • Specific meiotic substrate not identified
  3. 2000 Medium

    Linking BLM to the ATM-dependent DNA damage checkpoint: BLM accumulates in a phosphorylated form after IR in an ATM-dependent manner, and BLM-deficient cells partially escape the G2/M checkpoint.

    Evidence Phosphorylation-shift Western blot in ATM-deficient cells; cell cycle analysis by flow cytometry

    PMID:11146546

    Open questions at the time
    • Specific phosphorylation sites not mapped in this study
    • Mechanism of checkpoint contribution not defined
  4. 2001 High

    Establishing BLM as an anti-recombinase: elevated SCE in BLM-deficient DT40 cells depends on RAD54, and BLM physically interacts with RAD51, demonstrating that BLM suppresses RAD51/RAD54-dependent homologous recombination.

    Evidence BLM−/−/RAD54−/− double knockout DT40 epistasis; Co-IP and in vitro pulldown of BLM-RAD51; SCE and targeted integration assays

    PMID:10880455 PMID:11278509

    Open questions at the time
    • Mechanistic basis by which BLM opposes RAD51 loading not yet defined
    • Whether anti-recombinase function is helicase-dependent
  5. 2001 High

    Connecting BLM to p53-mediated apoptosis and defining the Topo IIIα interaction domain: BLM N-terminal 133 residues recruit Topo IIIα to PML bodies, and BLM is required for p53-dependent apoptosis, expanding BLM's role beyond recombination suppression.

    Evidence GFP-BLM deletion constructs in BS cells with SCE assay; Co-IP and apoptosis assays for p53 interaction

    PMID:11399766 PMID:11406610

    Open questions at the time
    • How p53 binding modulates BLM enzymatic activity in cells
    • Whether apoptotic role is independent of recombination control
  6. 2002 High

    Dissecting ATM phosphorylation sites and their functional specificity: ATM phosphorylates BLM at Thr99 after irradiation, which corrects radiosensitivity but not SCE, separating BLM's damage-response and recombination-suppression functions.

    Evidence Phosphospecific antibodies, stable cell lines with phospho-mutant BLM, functional rescue assays

    PMID:12034743

    Open questions at the time
    • Other kinases/sites contributing to damage response
    • Whether Thr99 phosphorylation alters BLM protein interactions
  7. 2002 High

    Defining p53 as a direct modulator of BLM helicase activity: purified p53 inhibits BLM Holliday junction unwinding, and this inhibition is abolished by p53 phosphorylation, revealing phosphorylation-dependent tuning of recombination intermediate processing.

    Evidence In vitro helicase assay with recombinant p53 and BLM; phosphopeptide analysis

    PMID:12080066

    Open questions at the time
    • In vivo relevance of p53-mediated helicase inhibition at specific genomic loci
    • Structural basis of p53-BLM interaction
  8. 2004 High

    Positioning BLM in the replication stress signaling hierarchy: 53BP1 and ATR/Chk1 are required for BLM recruitment to stalled forks, while BLM recruits 53BP1 independently of helicase activity, and telomere-binding proteins TRF1/TRF2 differentially regulate BLM unwinding.

    Evidence Co-IP, siRNA/kinase inhibitor experiments, helicase-dead BLM mutant; in vitro helicase assays with TRF1/TRF2

    PMID:15229185 PMID:15364958 PMID:15539948

    Open questions at the time
    • Whether TRF1/TRF2 regulation of BLM is phosphorylation-dependent
    • How BLM recruits 53BP1 without helicase activity
  9. 2006 High

    Reconstituting the dissolvasome and defining MPS1-PLK1 mitotic regulation: BLM–Topo IIIα–BLAP75 dissolve double Holliday junctions in a BLAP75-dependent manner; MPS1 phosphorylation at Ser144 creates a PLK1 docking site essential for spindle checkpoint maintenance and accurate chromosome segregation.

    Evidence In vitro dHJ dissolution with purified proteins; in vitro kinase assay, S144A mutant with mitotic arrest and chromosome number analysis

    PMID:16595695 PMID:16864798

    Open questions at the time
    • How PLK1 binding modifies BLM activity at centromeres
    • Whether BLAP75 undergoes its own regulatory modifications
  10. 2007 High

    Revealing BLM's role in anaphase ultrafine bridge (UFB) resolution: BLM with Topo IIIα and RMI1 localizes to centromere-connecting UFBs, and BLM deficiency increases anaphase bridges, establishing BLM in sister chromatid decatenation.

    Evidence Immunofluorescence live/fixed imaging with isogenic BLM-corrected cell lines

    PMID:17599064

    Open questions at the time
    • Substrate identity of centromeric UFBs (catenanes vs. recombination intermediates)
    • Whether BLM helicase or decatenase activity is rate-limiting
  11. 2009 High

    Uncovering SUMOylation as a pro-/anti-recombinogenic switch and defining single-molecule unwinding dynamics: SUMO-modified BLM preferentially recruits RAD51 to damaged forks (pro-recombinogenic), while unmodified BLM suppresses recombination; single-molecule FRET reveals monomeric BLM performs repetitive unwinding with RPA-dependent reinitiation.

    Evidence SUMO-site mutant BLM cell lines with SCE/RAD51 assays; smFRET on forked DNA substrates

    PMID:19165145 PMID:19956565

    Open questions at the time
    • SUMO ligase responsible for BLM modification not identified
    • Whether repetitive unwinding occurs on physiological substrates in vivo
  12. 2010 High

    Extending BTR complex function to ssDNA decatenation: Topo IIIα acts as a ssDNA decatenase specifically stimulated by BLM-RMI1, broadening the complex's activity beyond Holliday junction dissolution.

    Evidence In vitro ssDNA catenane decatenation assay with purified proteins

    PMID:20445207

    Open questions at the time
    • In vivo substrates of ssDNA decatenation not identified
    • Whether RMI2 further stimulates this activity
  13. 2011 High

    Linking BLM to rDNA transcription and Topo IIα cooperation: BLM unwinds GC-rich rDNA-like impediments and interacts with RNA Pol I subunit RPA194 to promote rRNA synthesis; separately, BLM interacts with Topo IIα (aa 489–587) in G2/M to prevent chromosome breakage.

    Evidence Co-IP, 3H-uridine pulse-chase, in vitro helicase on rDNA substrates; domain mapping of Topo IIα interaction with functional rescue

    PMID:21224348 PMID:22106380

    Open questions at the time
    • Whether rDNA role is independent of BTR complex
    • Structural basis of BLM–Topo IIα interaction
  14. 2013 High

    Defining cell-cycle-dependent BLM stability control and FANCD2 as an essential BLM regulator: MIB1 ubiquitinates BLM for G1 degradation while TopBP1 stabilizes it in S phase; FANCD2 maintains BLM stability, promotes BTR complex assembly, and recruits it to replicating chromatin for fork restart.

    Evidence MIB1 ubiquitination assay, TopBP1 knockdown/rescue, cell cycle fractionation; FANCD2 vs. FANCI knockdown epistasis, chromatin fractionation, fork restart assay

    PMID:23658231 PMID:24239288

    Open questions at the time
    • Whether MIB1 and FANCD2 pathways intersect
    • How FANCD2 senses replication stress to recruit BTR
  15. 2014 High

    Structural basis for BLM's G-quadruplex recognition and branch-point unwinding: crystal structure shows the RQC β-wing hairpin unpairs base pairs at dsDNA termini; RQC and HRDC domains cooperate to recognize G4 via flanking ssDNA binding.

    Evidence X-ray crystallography of BLM RQC–DNA complex; smFRET on G4-containing substrates with domain mutants

    PMID:25400656 PMID:25418155

    Open questions at the time
    • Full-length BLM structure on a G4 substrate not available
    • How G4 recognition is coordinated with helicase translocation in vivo
  16. 2017 High

    Establishing BLM as an R-loop resolvase, long-range resection helicase, and direct anti-recombinase against RAD51 loading: BLM unwinds R-loops and suppresses R-loop-associated instability; CtIP stimulates BLM-DNA2 for end resection; BLM ablation rescues HR in BRCA1/BRCA2/XRCC2-deficient cells by allowing RAD51 accumulation; TopBP1 BRCT4/5 crystal structure reveals pSer304 recognition.

    Evidence In vitro R-loop unwinding, proximity ligation assay; reconstituted BLM-DNA2-CtIP resection; BLM KO in HR-deficient backgrounds with RAD51 foci/HR reporter; X-ray crystallography of TopBP1-BLM peptide

    PMID:28912125 PMID:28919440 PMID:29020620 PMID:29042409

    Open questions at the time
    • Whether R-loop and resection roles are coordinated or independent
    • Relative contribution of BLM vs. EXO1 resection pathways in vivo
  17. 2018 High

    Defining biphasic DSB recruitment via MRN/ATM/RNF8 and HERC2 regulation of RPA–BLM–G4 axis: early BLM recruitment requires ATM; late retention requires MRE11 exonuclease and RNF8-dependent polyubiquitination with NBS1 interaction; HERC2 ubiquitinates RPA2 to cycle RPA off BLM complexes, preventing G4 accumulation.

    Evidence Laser micro-irradiation with kinase/nuclease inhibitors, ChIP, cell-cycle-specific analysis; HERC2 CRISPR knockout, G4 immunofluorescence, epistasis

    PMID:29523790 PMID:30279242

    Open questions at the time
    • Identity of the RNF8 ubiquitin chain type on BLM
    • Whether HERC2-RPA regulation is specific to G4 resolution
  18. 2019 High

    Delineating BLM's telomeric functions in ALT: BLM acts on lagging-strand telomere intermediates when ATRX is absent; SLX4IP antagonizes promiscuous BTR dissolution at ALT telomeres; FANCM-dependent R-loop resolution counteracts BLM-driven replication stress; single-molecule DNA curtains confirm RAD51-on-DNA blocks BLM, and PLK1 restrains BLM unwinding at centromeres.

    Evidence BLM ChIP and ssDNA analysis at telomeres; SLX4IP/SLX4 double KO synthetic lethality rescued by BLM loss; FANCM/BLM co-depletion with RNaseH1 rescue; DNA curtains; PLK1 inhibitor with BLM knockdown rescue

    PMID:31138795 PMID:31253795 PMID:31447390 PMID:31544923 PMID:38593805

    Open questions at the time
    • How BLM substrate selection differs between centromeres and ALT telomeres
    • Whether PLK1-mediated suppression of BLM at centromeres involves direct phosphorylation beyond Ser144
  19. 2020 High

    Revealing RPA-enabled bidirectional unwinding at nicks and CDK/PLK1 phosphorylation-dependent helicase tuning: RPA activates BLM at nicks for bidirectional unwinding without requiring direct BLM-RPA interaction; CDK phosphorylation of Sgs1/BLM enhances helicase velocity while subsequent PLK1 hyperphosphorylation reduces it, ordering noncrossover/crossover resolution.

    Evidence Optical tweezers + fluorescence single-molecule assay at nicks; in vitro helicase assay of phospho-Sgs1 with joint molecule analysis in yeast

    PMID:32101168 PMID:32504558

    Open questions at the time
    • Whether human BLM velocity is similarly regulated by CDK
    • In vivo nick sites where bidirectional unwinding operates
  20. 2021 Medium

    Identifying USP37 as a damage-responsive BLM deubiquitinase: ATM phosphorylates USP37, enhancing its interaction with BLM and counteracting polyubiquitination, thus stabilizing BLM for DNA damage response.

    Evidence Co-IP, deubiquitination assay, ATM inhibitor, knockdown with functional rescue

    PMID:34606619

    Open questions at the time
    • Relationship between USP37 and TopBP1 stabilization pathways
    • Whether USP37 targets the same ubiquitin chains as MIB1
  21. 2025 Medium

    Discovering lactylation as a novel BLM regulatory modification: AARS1 lactylates BLM at Lys24 in response to chemotherapy, inhibiting MIB1-mediated ubiquitination, stabilizing BLM, and promoting HR-mediated repair.

    Evidence Global lactylome, lactylation/ubiquitination assays, HR reporter, BLM K24 mutant expression

    PMID:40634292

    Open questions at the time
    • Whether lactylation occurs under physiological (non-chemotherapy) conditions
    • Interplay between Lys24 lactylation and nearby SUMOylation sites
    • Independent replication needed

Open questions

Synthesis pass · forward-looking unresolved questions
  • Several mechanistic questions remain open: the SUMO E3 ligase modifying BLM is unidentified; a full-length BLM structure on physiological substrates is lacking; how BLM switches between pro-recombinogenic (fork restart/resection) and anti-recombinogenic (RAD51 displacement) modes at the same locus is not resolved; and the in vivo substrates of BLM-Topo IIIα ssDNA decatenation remain undefined.
  • No SUMO E3 ligase identified for BLM
  • No full-length BLM cryo-EM or crystal structure
  • Mechanism governing pro- vs. anti-recombinogenic switch at individual loci unknown
  • In vivo decatenation substrates not defined

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140657 ATP-dependent activity 7 GO:0140097 catalytic activity, acting on DNA 4 GO:0003677 DNA binding 3 GO:0140098 catalytic activity, acting on RNA 3
Localization
GO:0005634 nucleus 3 GO:0005694 chromosome 3 GO:0005730 nucleolus 1
Pathway
R-HSA-73894 DNA Repair 6 R-HSA-1640170 Cell Cycle 4 R-HSA-69306 DNA Replication 4 R-HSA-8953854 Metabolism of RNA 3
Partners
FANCD2POT1RAD51RMI1TOP3ATOPBP1TP53TRF2
Complex memberships
BLM-DNA2-CtIP resection complexBTR dissolvasome (BLM-Topo IIIα-RMI1/RMI2)

Evidence

Reading pass · 55 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2006 BLM, topoisomerase IIIα, and BLAP75 form a 'dissolvasome' complex that dissolves double Holliday junctions (dHJ) to yield non-crossover recombinants; BLAP75 associates independently with both Topo IIIα and BLM, and under physiological conditions dHJ dissolution becomes completely dependent on BLAP75. This activity is specific to BLM (not RecQ or WRN with Topo IIIα). In vitro reconstitution with highly purified human proteins; double Holliday junction dissolution assay The Journal of biological chemistry High 16595695
2008 BLAP75's evolutionarily conserved N-terminal third mediates complex formation with BLM and Topo IIIα and is sufficient to promote dHJ dissolution and HJ unwinding by BLM-Topo IIIα; the BLAP75 DNA-binding activity (C-terminal third) is dispensable for HJ processing in vitro. A BLAP75 point mutant (K166A) defective in Topo IIIα interaction cannot promote dHJ dissolution. In vitro biochemical assays with BLAP75 deletion fragments and point mutants; dHJ dissolution and HJ branch migration assays The Journal of biological chemistry High 18390547
2010 Human topoisomerase IIIα is a single-stranded DNA decatenase that is specifically stimulated by the BLM-RMI1 pair; RMI1 interacts with Topo IIIα and this interaction is required for the stimulatory effect on decatenase activity. In vitro single-stranded catenane decatenation assay with purified proteins; interaction mapping The Journal of biological chemistry High 20445207
2001 Purified BLM and human RAD51 interact in vitro and in vivo; residues in the N- and C-terminal domains of BLM independently mediate this interaction. BLM localizes to a subset of RAD51 nuclear foci; exogenous BLM expression reduces the fraction of cells with RAD51 foci. The BLM-RAD51 interaction is evolutionarily conserved (Sgs1 C-terminal domain interacts with yeast Rad51). SGS1 and RAD51 are epistatic. Co-immunoprecipitation, in vitro pulldown, immunofluorescence co-localization, genetic epistasis analysis The Journal of biological chemistry High 11278509
2007 BLM-defective cells display elevated anaphase bridges and lagging chromatin. In normal cells, BLM localizes to anaphase bridges and colocalizes with Topo IIIα and hRMI1 (BLAP75). BLM staining identifies a class of ultrafine DNA bridges (also staining for PICH) that frequently link centromeric loci and are elevated in BLM-deficient cells, indicating BLM ensures complete sister chromatid decatenation in anaphase. Immunofluorescence live and fixed cell imaging; isogenic BLM-corrected cell lines as controls The EMBO journal High 17599064
2001 The first 133 amino acids of BLM are necessary and sufficient for interaction with Topo IIIα; Topo IIIα is recruited to PML nuclear bodies via its interaction with BLM. Expression of BLM lacking amino acids 1-133 (Topo IIIα-interaction domain) results in intermediate SCE reduction, implicating the BLM-Topo IIIα complex in regulating somatic recombination. GFP-tagged BLM deletion constructs expressed in BS cells; sister chromatid exchange (SCE) assay; co-immunoprecipitation; immunofluorescence Human molecular genetics High 11406610
2002 BLM directly interacts with ATM in vivo; BLM is phosphorylated in a mitosis-dependent manner partly dependent on ATM. Phosphorylation at Thr-99 is radiation-induced and defective in ataxia-telangiectasia cells. Phosphorylation site mutants of BLM fail to correct radiosensitivity but do correct SCE, indicating that ATM-mediated BLM phosphorylation specifically mediates the radiation-damage response but not SCE suppression. Co-immunoprecipitation, phosphospecific antibodies, stable cell lines expressing phosphorylation mutants, functional rescue assays The Journal of biological chemistry High 12034743
2006 BLM is phosphorylated at Ser144 by the spindle assembly checkpoint kinase MPS1. Phosphorylated BLM (pSer144) then interacts with the polo-box domain of PLK1. BS cells expressing BLM-S144A fail to maintain mitotic arrest when the spindle assembly checkpoint is activated and exhibit broad chromosome number distribution, demonstrating that MPS1-dependent BLM phosphorylation is important for accurate chromosome segregation. Co-immunoprecipitation, in vitro kinase assay, stable expression of phosphorylation site mutant, mitotic arrest assay, chromosome number analysis Proceedings of the National Academy of Sciences of the United States of America High 16864798
2009 SUMO modification of BLM controls the switch between its pro- and anti-recombinogenic roles at damaged replication forks. SUMO-mutant BLM (SM-BLM) cells accumulate DNA breaks, are hypersensitive to damage, and fail to induce sister-chromatid exchanges upon HU treatment. RAD51 localization to HU-induced foci is impaired in SM-BLM cells. RAD51 interacts noncovalently with SUMO and interacts more efficiently with SUMO-modified BLM than unmodified BLM. Stable cell lines with SUMO-site mutant BLM, SCE assay, γ-H2AX foci, RAD51 focus formation, in vitro interaction of SUMO with RAD51, co-immunoprecipitation PLoS biology High 19956565
2009 BLM undergoes repetitive unwinding on forked DNA substrates at the single-molecule level: a monomeric BLM unwinds a defined length of duplex DNA, then reverses via strand switching and re-initiates. hRPA interaction with BLM is necessary for unwinding reinitiation on hRPA-coated DNA. Single-molecule FRET (smFRET) microscopy on individual DNA molecules The EMBO journal High 19165145
2014 BLM interacts with intra-strand G-quadruplex (G4) structures via cooperativity between its RQC and HRDC domains: the RQC domain binds G4, stabilized by HRDC binding to flanking ssDNA. A short ssDNA segment separating G4 from dsDNA is a key regulator of BLM activity on G4 substrates. Single-molecule FRET; structure-function analysis of BLM domain mutants on G4-containing substrates Nature communications High 25418155
2014 Crystal structure of BLM bound to DNA reveals that the RQC domain recognizes, binds, and unwinds DNA at branch points, with the β-wing hairpin in the RQC winged-helix motif acting to unpair Watson-Crick base pairs at the DNA duplex terminus, similar to WRN. Crystal structure (X-ray crystallography) of BLM RQC domain-DNA complex Frontiers in genetics Medium 25400656
2003 p53 and BLM physically associate and co-localize with RAD51 at sites of HU-stalled replication forks. BLM is required for efficient localization of p53 to these foci and for physical association of p53 with RAD51. Loss of BLM and p53 synergistically enhances homologous recombination, indicating they act in complementary pathways. p53 involvement in regulating spontaneous SCE is BLM-dependent. Co-immunoprecipitation, immunofluorescence co-localization, SCE assay, siRNA/genetic knockout analysis The EMBO journal High 12606585
2002 Purified recombinant p53 binds to BLM and WRN helicases in vitro and attenuates their ability to unwind synthetic Holliday junctions. Phosphorylation at Ser376 or Ser378 of p53 abolishes this inhibition. Following replication fork blockage, pSer15-p53, BLM, and RAD51 co-localize in nuclear foci. In vitro helicase assay with recombinant proteins, pulldown/binding assays, phosphopeptide analysis, immunofluorescence The Journal of biological chemistry High 12080066
2001 BLM binds p53 in vivo and in vitro via the C-terminal domain of p53. BLM is required for p53-mediated apoptosis: BS fibroblasts are defective in p53-dependent apoptosis rescued by wild-type BLM. BLM localizes to PML nuclear bodies (NBs); functional p53 promotes BLM accumulation in NBs. BLM mutants that fail to localize to NBs act in a dominant-negative fashion to block p53-mediated apoptosis. Co-immunoprecipitation, in vitro binding, apoptosis assays, immunofluorescence, dominant-negative mutant analysis The Journal of biological chemistry High 11399766
2005 POT1 strongly stimulates BLM (and WRN) to unwind long telomeric forked duplexes and D-loop structures in a telomeric-sequence-dependent manner. Purified POT1 binds to BLM in vitro. This stimulation is not seen with a bacterial helicase. In vitro helicase assay with purified proteins on telomeric substrates; pulldown binding assay The Journal of biological chemistry High 16030011
2004 TRF1 and TRF2 directly interact with BLM and regulate its unwinding activity in vitro: TRF2 stimulates BLM unwinding of both telomeric and non-telomeric substrates, while TRF1 inhibits BLM unwinding of telomeric substrates only. TRF2 stimulates BLM activity even with equimolar TRF1 but not when TRF1 is in molar excess. BLM co-localizes and co-immunoprecipitates with TRF2 in ALT cells. In vitro helicase assay with purified proteins, co-immunoprecipitation, immunofluorescence co-localization Human molecular genetics High 15229185
2004 BLM is an intermediate responder to stalled replication forks, co-localizing and physically interacting with 53BP1 and γH2AX. 53BP1 is required for efficient accumulation of BLM and p53 at stalled replication sites. Active Chk1 kinase is essential for accurate colocalization of 53BP1 with BLM and for BLM stabilization. Chk1-mediated signaling places BLM downstream of ATR in the replication stress response. Co-immunoprecipitation, immunofluorescence, siRNA knockdown, kinase inhibitor experiments The Journal of cell biology High 15364958
2004 BLM rapidly moves from PML nuclear bodies to damaged replication forks upon replication stress, then returns to PML bodies, controlled by ATR (for relocalization to forks) and ATM (for return to PML bodies). BLM-deficient fibroblasts are deficient in phospho-ATM (S1981) and 53BP1 foci following replication stress. BLM recruits 53BP1 to stalled forks independent of its helicase activity. Immunofluorescence, cellular fractionation, kinase inhibitor treatment, helicase-dead BLM mutant expression Cell cycle (Georgetown, Tex.) Medium 15539948
2013 TopBP1 interacts with BLM in a phosphorylation- and cell-cycle-dependent manner to regulate BLM protein stability. In S phase, TopBP1 protects BLM from MIB1 E3 ligase-mediated ubiquitination and degradation. TopBP1 depletion decreases BLM protein level and increases SCE. An undegradable BLM mutant causes radiation sensitivity by promoting end resection and inhibiting NHEJ in G1. Co-immunoprecipitation, ubiquitination assay, siRNA knockdown, SCE assay, cell cycle analysis, mutant BLM expression Molecular cell High 24239288
2017 TopBP1 BRCT4/5 specifically interacts with BLM phospho-Ser304 (not pSer338); crystal structure reveals pSer304 recognition by a conserved pSer-binding pocket and an FVPP motif of BLM engaging a hydrophobic groove on BRCT5. This uses the same BRCT5 surface that recognizes MDC1 but with reversed binding orientation. Crystal structure (X-ray crystallography) of TopBP1 BRCT4/5 bound to BLM pSer304 peptide; biochemical binding assays Structure (London, England : 1993) High 28919440
2001 The C-terminus of BLM directly interacts with MLH1 (confirmed by yeast two-hybrid, far Western, and co-immunoprecipitation). However, cell extracts deficient in BLM are competent for DNA mismatch repair, indicating BLM and MLH1 function together in a recombination or repair event independent of single-base mismatch repair. Yeast two-hybrid, far Western, co-immunoprecipitation, in vitro mismatch repair assay The Journal of biological chemistry Medium 11325959
2004 The recombinant hMSH2/6 complex stimulates BLM's ability to process Holliday junctions in vitro, an activity also regulated by p53. hMSH2 and hMSH6 co-immunoprecipitate with BLM, p53, and RAD51. Increased RAD51 foci and BLM-p53-RAD51 complex levels are found in hMSH2- or hMSH6-deficient cells. In vitro Holliday junction processing assay, co-immunoprecipitation, immunofluorescence Oncogene Medium 15064730
1997 BLM protein is transported to the nucleus via a bipartite nuclear localization signal (NLS) in the C-terminus (residues 1334-1349). The distal arm of the bipartite basic residues is essential for nuclear targeting; truncation at residue 1341 (retaining only the proximal arm) prevents nuclear localization. EGFP-fusion constructs of full-length and deleted BLM expressed in HeLa cells; immunofluorescence Biochemical and biophysical research communications High 9388480
2000 BLM is phosphorylated and accumulates in an ATM-dependent manner in response to ionizing radiation. BLM-deficient cells show partial escape from the γ-irradiation-induced G2/M checkpoint, positioning BLM as a downstream effector of ATM kinase in the DNA damage response. Western blot with phosphorylation-shift assay, ATM inhibitor/ATM-deficient cells, cell cycle analysis by flow cytometry Oncogene Medium 11146546
2006 BLM's HRDC domain (specifically residues 1250-1292) is sufficient for early recruitment to laser-induced DNA double-strand breaks, with accumulation detectable within 10 seconds. Early BLM accumulation is independent of ATM, RAD17, DNA-PKcs, NBS1, XRCC3, RAD52, RAD54, or WRN. Laser micro-irradiation, live-cell imaging of GFP-tagged BLM domain truncations, genetic knockout DT40 cells Biochemical and biophysical research communications Medium 16876111
2018 MRN complex (NBS1, MRE11) is required for biphasic BLM recruitment to DSBs: ATM activity is essential for early-phase recruitment, while MRE11 exonuclease activity and RNF8-mediated ubiquitylation of BLM are key for late-phase retention. Interaction between polyubiquitylated BLM and NBS1 retains BLM at DSBs. BLM helicase activity is required for recruitment of HR factors in S phase and c-NHEJ factors in G1; BLM inhibits HR in S phase and c-NHEJ in G1. Co-immunoprecipitation, ubiquitylation assay, siRNA knockdown, laser micro-irradiation, ChIP, cell-cycle-specific analysis Nature communications High 29523790
2001 In BLM-deficient cells (DT40), increased SCE frequency is substantially reduced and enhanced targeted integration is abolished in BLM(-/-)/RAD54(-/-) double mutants, demonstrating that SCE in BLM-deficient cells occurs predominantly via homologous recombination and that BLM normally suppresses RAD54-dependent homologous recombination. Genetic epistasis using BLM(-/-)/RAD54(-/-) DT40 double knockout cells; SCE assay, targeted integration frequency The EMBO journal High 10880455
2017 BLM promotes long-range DNA end resection via the BLM-DNA2 pathway, independently of its Holliday junction processing role. CtIP interacts with BLM and enhances its helicase activity; CtIP also enhances DNA2 cleavage, establishing CtIP as a stimulator of long-range resection through BLM-DNA2. In vitro helicase and nuclease assays with purified proteins; co-immunoprecipitation Cell reports High 29020620
2017 BLM helicase acts as an anti-recombinase by counteracting RAD51 loading at DSBs. Ablation of BLM in cells with mutant BRCA1, or cells lacking BRCA2 or XRCC2, substantially increases RAD51 stability at DSBs and overall HR efficiency, rescuing genomic integrity and cell survival. siRNA/genetic knockout of BLM combined with BRCA1 mutant or BRCA2/XRCC2 KO cells; RAD51 foci, HR reporter assay The Journal of cell biology High 28912125
2013 FANCD2 is an essential regulator of the BLM complex: it maintains BLM protein stability, is crucial for complete BLM complex (BLMcx) assembly, recruits BLMcx to replicating chromatin during S phase, and mediates phosphorylation of BLMcx members upon DNA damage. FANCD2 and BLM cooperate to promote restart of stalled replication forks while suppressing new origin firing. FANCI is dispensable for these functions. Co-immunoprecipitation, chromatin fractionation, siRNA knockdown of FANCD2 vs. FANCI, replication fork restart assay, BLM stability assay Nucleic acids research High 23658231
2004 BLM co-localizes and co-immunoprecipitates with FANCD2 following DNA crosslinker or replication fork stall treatment. The FA core complex is necessary for BLM phosphorylation and nuclear focus assembly in response to crosslinked DNA, placing BLM downstream of the FA core complex in a pathway for S-phase checkpoint activation. Co-immunoprecipitation, immunofluorescence, siRNA knockdown of FA core complex members, BLM phosphorylation assay The EMBO journal High 15257300
2011 BLM directly interacts with and co-localizes with topoisomerase IIα via amino acids 489-587 of BLM, predominantly in late G2 and M phases. Deletion of this region does not affect intrinsic BLM helicase activity but abolishes Topo IIα-dependent enhancement of BLM activity. This interaction is required to prevent elevated chromosome breakage in BLM-deficient cells. Co-immunoprecipitation, in vitro interaction with deletion constructs, in vitro helicase assay, chromosome breakage assay in transfected BS cells Cancer research High 21224348
2011 BLM co-immunoprecipitates with RPA194 (a subunit of RNA polymerase I) in vivo. BLM is required for efficient rRNA transcription (demonstrated by 3H-uridine pulse-chase). In vitro, BLM unwinds GC-rich rDNA-like substrates that form in the nucleolus and impede RNA Pol I. BLM nucleolar localization depends on ongoing RNA Pol I transcription. Co-immunoprecipitation, 3H-uridine pulse-chase assay, in vitro helicase assay on rDNA substrates, immunofluorescence Human molecular genetics High 22106380
2012 DNA topoisomerase I directly interacts with the C-terminus of BLM. Topo I stimulates BLM helicase activity on RNA:DNA hybrid substrates (but not DNA:DNA duplexes), and reciprocally BLM enhances Topo I relaxation activity on supercoiled DNA, suggesting coordinated function in rDNA transcription. Co-immunoprecipitation, in vitro IVTT interaction, in vitro helicase assay on RNA:DNA hybrid, Topo I relaxation assay Mutation research Medium 23261817
2001 BLM is cleaved to 47- and 110-kDa fragments during apoptosis by caspase 3, not caspase 6. Mutation of the caspase 3 recognition sequence (D415G) renders BLM resistant to cleavage. Caspase 3 cleavage does not abolish BLM helicase activity but abolishes BLM nuclear foci and association with condensed DNA and the insoluble nuclear matrix. In vitro caspase cleavage assay with recombinant BLM, site-directed mutagenesis of D415, immunofluorescence, cellular fractionation The Journal of biological chemistry High 11154689
2017 BLM/Sgs1 suppresses R-loop-associated genome instability. Loss of SGS1 increases R-loop accumulation and γ-H2A at replication pausing regions and long genes. BLM is found physically proximal to DNA:RNA hybrids in human cells. BLM can efficiently unwind R-loops in vitro. BLM depletion in human cells increases R-loop-associated instability. In vitro helicase assay on R-loop substrates; proximity ligation assay (BLM/DNA:RNA hybrids); sequencing of sgs1Δ mutation spectrum; BLM depletion in Bloom's syndrome fibroblasts The Journal of cell biology High 29042409
2012 BLM and RECQL4 interact physically in vivo and in vitro. The BLM-interacting domain of RECQL4 maps to amino acids 361-478; the region of BLM encompassing amino acids 1-902 interacts with RECQL4. RECQL4 specifically stimulates BLM helicase activity on DNA fork substrates in vitro. The interaction is enhanced during S phase and after ionizing radiation. Depletion of RECQL4 in BLM-deficient cells reduces proliferative capacity and increases SCE. Co-immunoprecipitation, in vitro pulldown with domain mapping, in vitro helicase assay, SCE assay Nucleic acids research Medium 22544709
2009 BLM interacts with RAD54 via an internal 10-residue N-terminal polypeptide of BLM. The BLM N-terminal region prevents RAD51-RAD54 complex formation in vitro and in vivo. BLM enhances the ATPase and chromatin-remodeling activities of RAD54, and increases mobility of chromatin-associated RAD51. An ATPase-dead BLM mutant still enhances RAD54 activities, indicating this is helicase-independent. Co-immunoprecipitation, in vitro interaction with peptides, ATPase assay, chromatin remodeling assay, FRAP Journal of cell science Medium 19671661
2019 BLM localization to ALT telomeres is permissive when ATRX is absent. BLM helicase acts on lagging-strand telomere intermediates (C-strand-specific ssDNA) in ALT-positive cells. DNA2 deficiency increases 5'-flap formation in a BLM-dependent manner. Telomere C-strand (but not G-strand) nicks promote ALT, linking BLM-directed HDR to aberrant lagging strand replication. BLM ChIP, single-strand DNA analysis, DNA2/ATRX knockouts, nick-induction assays at telomeres Molecular cell High 38593805
2019 SLX4IP accumulates at ALT telomeres and interacts with SLX4, XPF, and BLM. Loss of SLX4IP increases ALT phenotypes; concomitant loss of SLX4 and SLX4IP is incompatible with growth. BLM inactivation rescues telomere aggregation and synthetic lethality in SLX4IP/SLX4 double-deficient cells, indicating SLX4IP antagonizes promiscuous BLM dissolution activity to balance SMX resolution and BTR dissolution at ALT telomeres. Co-immunoprecipitation, genetic knockouts, ALT assay, telomere analysis Molecular cell High 31447390
2019 FANCM depletion in ALT cells induces telomere replication stress; depletion of BLM reduces this replication stress and associated proliferation defects. FANCM unwinds telomeric R-loops in vitro and suppresses their accumulation in cells. Overexpression of RNaseH1 abolishes replication stress in FANCM/BLM co-depleted cells, indicating BLM's role is upstream of R-loop-driven replication stress at ALT telomeres. siRNA knockdown, in vitro R-loop unwinding assay, RNaseH1 overexpression rescue, telomere dysfunction assays Nature communications High 31138795
2013 BLM helicase can unwind RNA G-quadruplex (rG4) structures; BLM is recruited to cytoplasmic stress granules (SGs) in an rG4-dependent manner and under multiple stress conditions. BLM acts as a negative regulator of SG formation. Immunofluorescence and live imaging of BLM in SGs; in vitro rG4 unwinding assay; stress granule assay under varying conditions Nucleic acids research Medium 37503837
2019 BLM visualized at single-molecule level on DNA curtains is a robust helicase (70-80 bp/sec, ~8-10 kb processivity on dsDNA). BLM cannot translocate on RPA-coated ssDNA. RAD51 on ssDNA blocks BLM association and translocation; RAD51 on dsDNA also blocks BLM translocation, supporting an anti-recombinase mechanism. Single-molecule DNA curtains visualization with fluorescence microscopy Nucleic acids research High 31544923
2020 Human RPA (hRPA) not only enables BLM to unidirectionally unwind nicked dsDNA under reduced force but also permits bidirectional unwinding of nicked dsDNA. This activation requires BLM targeting to the nick and free hRPA in solution; direct interactions between BLM and hRPA are dispensable for activation. Combined single-molecule approach (optical tweezers + fluorescence); nick-specific unwinding assay eLife High 32101168
2021 The deubiquitinating enzyme USP37 interacts with BLM, deubiquitinates and stabilizes BLM. DNA DSBs promote ATM-mediated phosphorylation of USP37, enhancing USP37-BLM binding. USP37 knockdown increases BLM polyubiquitination, accelerates its proteolysis, and impairs DNA damage response. Co-immunoprecipitation, deubiquitination assay, ATM inhibitor treatment, knockdown with functional rescue Nucleic acids research Medium 34606619
2013 MIB1 E3 ubiquitin ligase ubiquitinates BLM, targeting it for degradation in G1 cells; TopBP1 stabilizes BLM in S phase by antagonizing MIB1-mediated ubiquitination. This degradation/stabilization cycle ensures BLM-dependent end resection (which inhibits NHEJ) is restricted to S phase. Ubiquitination assay, MIB1 knockdown/rescue, cell cycle fractionation, BLM stability measurement Molecular cell High 24239288
2019 PLK1 inhibition causes BLM helicase to unlawfully unwind DNA at centromeres, leading to centromere disintegration (distortion into threadlike DNA molecules under spindle tension) and chromosome arm splitting. PLK1 normally suppresses BLM's unwinding activity at centromeres to maintain centromere integrity during biorientation. PLK1 inhibitor treatment, BLM knockdown rescue, live-cell imaging, CRISPR knockout cells Nature communications High 31253795
2008 BLM and RECQ1 display distinct substrate specificities: BLM unwinds G-quadruplexes, RNA-DNA hybrids, and regresses model replication forks; RECQ1 cannot perform these activities. RECQ1 can resolve immobile Holliday junctions lacking a homologous core without RPA. BLM N-terminus (residues 1-56) required for RECQ1 oligomerization and its unique HJ activity. In vitro helicase assays on multiple DNA substrates; N-terminal deletion mutagenesis The Journal of biological chemistry High 18448429
2015 The RQC domain of BLM is involved in stabilizing interaction with the G4 structure via interaction with the ssDNA flanking G4; the Lys1125 residue in the RQC domain is important for backward sliding activity during unwinding of hairpin/G4 structures as shown by mutagenesis and magnetic tweezers experiments. Magnetic tweezers single-molecule assay; site-directed mutagenesis of BLM RQC domain Nucleic acids research Medium 25765643
2012 BLM functions as a monomer during DNA unwinding: BLM multimers dissociate upon ATP hydrolysis, and steady-state and single-turnover kinetics reveal monomeric BLM activity under varying enzyme/ATP concentrations and DNA tail lengths. ATPase measurements suggest monomers resolve Holliday junctions and D-loops. Dynamic light scattering, stopped-flow kinetics, single-turnover helicase assay, ATPase activity measurement Nucleic acids research Medium 22885301
2020 CDK-mediated phosphorylation of Sgs1 (BLM ortholog) enhances its helicase velocity and processivity during S phase/meiotic prophase I, stimulating joint molecule processing. Subsequent hyperphosphorylation by Cdc5/PLK1 reduces Sgs1 activity while activating crossover nucleases, providing ordered noncrossover/crossover resolution. In vitro helicase assay of phosphorylated vs. unphosphorylated Sgs1, joint molecule analysis in yeast, kinase mutant analysis Developmental cell High 32504558
2018 HERC2 (a HECT E3 ligase) interacts with BLM, WRN, and RPA complexes during S phase. HERC2 depletion dissociates RPA from BLM/WRN complexes and increases G4 DNA formation. HERC2's E3 ligase activity ubiquitinates RPA2, promoting its release from helicase complexes; loss of E3 activity causes RPA accumulation in helicase complexes and increased G4. HERC2 is epistatic to BLM/WRN in G4 suppression. Co-immunoprecipitation, siRNA triple depletion epistasis, CRISPR deletion of HERC2 catalytic domain, G4 immunofluorescence, in vitro RPA release assay Cancer research High 30279242
2025 BLM is lactylated at Lys24 by the lactyl-transferase AARS1 in response to chemotherapy. Hyperlactylation of BLM at Lys24 stabilizes BLM protein by inhibiting MIB1-mediated ubiquitination and increases its interaction with DNA repair factors, promoting DNA end resection and HR repair. Lys24 mutation (delactylation) impairs HR repair and increases anthracycline sensitivity. Global lactylome analysis, lactylation assay, ubiquitination assay, HR reporter assay, BLM Lys24 mutant expression Signal transduction and targeted therapy Medium 40634292
1999 BLM protein localizes to discrete foci along synaptonemal complexes (SCs) in mouse spermatocytes during late zygonema of meiotic prophase, co-localizing with replication protein A (RPA) with a temporal delay. BLM dissociates from SCs during pachynema. This suggests BLM is required for a late step in processing DNA intermediates during interhomolog interactions in early meiotic prophase. Immunocytological analysis (immunofluorescence) of mouse spermatocyte meiotic spreads; co-localization with SC markers and RPA Proceedings of the National Academy of Sciences of the United States of America Medium 10318934

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2007 BLM is required for faithful chromosome segregation and its localization defines a class of ultrafine anaphase bridges. The EMBO journal 354 17599064
2001 SGS1, the Saccharomyces cerevisiae homologue of BLM and WRN, suppresses genome instability and homeologous recombination. Nature genetics 283 11138010
2001 Potential role for the BLM helicase in recombinational repair via a conserved interaction with RAD51. The Journal of biological chemistry 241 11278509
2006 A double Holliday junction dissolvasome comprising BLM, topoisomerase IIIalpha, and BLAP75. The Journal of biological chemistry 202 16595695
2019 FANCM limits ALT activity by restricting telomeric replication stress induced by deregulated BLM and R-loops. Nature communications 184 31138795
2003 BLM helicase-dependent transport of p53 to sites of stalled DNA replication forks modulates homologous recombination. The EMBO journal 175 12606585
2019 The FANCM-BLM-TOP3A-RMI complex suppresses alternative lengthening of telomeres (ALT). Nature communications 164 31138797
2005 POT1 stimulates RecQ helicases WRN and BLM to unwind telomeric DNA substrates. The Journal of biological chemistry 157 16030011
2004 Association and regulation of the BLM helicase by the telomere proteins TRF1 and TRF2. Human molecular genetics 132 15229185
2008 The Human RecQ helicases, BLM and RECQ1, display distinct DNA substrate specificities. The Journal of biological chemistry 130 18448429
2007 Syndrome-causing mutations of the BLM gene in persons in the Bloom's Syndrome Registry. Human mutation 128 17407155
2000 Possible association of BLM in decreasing DNA double strand breaks during DNA replication. The EMBO journal 124 10880455
2017 FANCM, BRCA1, and BLM cooperatively resolve the replication stress at the ALT telomeres. Proceedings of the National Academy of Sciences of the United States of America 121 28673972
2001 Functional interaction of p53 and BLM DNA helicase in apoptosis. The Journal of biological chemistry 118 11399766
2002 Coexpression of ephrin-Bs and their receptors in colon carcinoma. Cancer 113 11920461
2001 Evidence for BLM and Topoisomerase IIIalpha interaction in genomic stability. Human molecular genetics 113 11406610
2004 Functional interaction between BLM helicase and 53BP1 in a Chk1-mediated pathway during S-phase arrest. The Journal of cell biology 112 15364958
2005 Recql5 and Blm RecQ DNA helicases have nonredundant roles in suppressing crossovers. Molecular and cellular biology 109 15831450
2002 Functional link between BLM defective in Bloom's syndrome and the ataxia-telangiectasia-mutated protein, ATM. The Journal of biological chemistry 109 12034743
2009 Activating systemic autoimmunity: B's, T's, and tolls. Current opinion in immunology 106 19800208
2009 SUMO modification regulates BLM and RAD51 interaction at damaged replication forks. PLoS biology 105 19956565
2002 The processing of Holliday junctions by BLM and WRN helicases is regulated by p53. The Journal of biological chemistry 104 12080066
2017 RECQ-like helicases Sgs1 and BLM regulate R-loop-associated genome instability. The Journal of cell biology 99 29042409
2004 BLM and the FANC proteins collaborate in a common pathway in response to stalled replication forks. The EMBO journal 98 15257300
2013 FANCD2 regulates BLM complex functions independently of FANCI to promote replication fork recovery. Nucleic acids research 90 23658231
2013 The BLM dissolvasome in DNA replication and repair. Cellular and molecular life sciences : CMLS 89 23543275
2001 The Bloom's syndrome protein (BLM) interacts with MLH1 but is not required for DNA mismatch repair. The Journal of biological chemistry 88 11325959
2014 Mechanistic insight into the interaction of BLM helicase with intra-strand G-quadruplex structures. Nature communications 87 25418155
1999 Bloom's syndrome protein, BLM, colocalizes with replication protein A in meiotic prophase nuclei of mammalian spermatocytes. Proceedings of the National Academy of Sciences of the United States of America 83 10318934
2009 Aging-associated dysfunction of Akt/protein kinase B: S-nitrosylation and acetaminophen intervention. PloS one 77 19641606
2017 BLM helicase regulates DNA repair by counteracting RAD51 loading at DNA double-strand break sites. The Journal of cell biology 76 28912125
2000 ATM-dependent phosphorylation and accumulation of endogenous BLM protein in response to ionizing radiation. Oncogene 75 11146546
2019 SLX4IP Antagonizes Promiscuous BLM Activity during ALT Maintenance. Molecular cell 74 31447390
2015 Deleterious Germline BLM Mutations and the Risk for Early-onset Colorectal Cancer. Scientific reports 70 26358404
2009 BLM helicase measures DNA unwound before switching strands and hRPA promotes unwinding reinitiation. The EMBO journal 66 19165145
2008 Functional role of BLAP75 in BLM-topoisomerase IIIalpha-dependent holliday junction processing. The Journal of biological chemistry 64 18390547
2010 Human topoisomerase IIIalpha is a single-stranded DNA decatenase that is stimulated by BLM and RMI1. The Journal of biological chemistry 63 20445207
2004 The mismatch DNA repair heterodimer, hMSH2/6, regulates BLM helicase. Oncogene 63 15064730
2017 Enhancement of BLM-DNA2-Mediated Long-Range DNA End Resection by CtIP. Cell reports 62 29020620
2018 EphBs and ephrin-Bs: Trans-synaptic organizers of synapse development and function. Molecular and cellular neurosciences 61 30031105
2014 Structural mechanisms of human RecQ helicases WRN and BLM. Frontiers in genetics 61 25400656
2018 MRN complex-dependent recruitment of ubiquitylated BLM helicase to DSBs negatively regulates DNA repair pathways. Nature communications 58 29523790
2004 ATR and ATM-dependent movement of BLM helicase during replication stress ensures optimal ATM activation and 53BP1 focus formation. Cell cycle (Georgetown, Tex.) 57 15539948
2006 MPS1-dependent mitotic BLM phosphorylation is important for chromosome stability. Proceedings of the National Academy of Sciences of the United States of America 56 16864798
2004 Genetic interactions between BLM and DNA ligase IV in human cells. The Journal of biological chemistry 56 15509577
2016 Bloom's syndrome: Why not premature aging?: A comparison of the BLM and WRN helicases. Ageing research reviews 55 27238185
2007 Role of the BLM helicase in replication fork management. DNA repair 54 17363339
1997 BLM (the causative gene of Bloom syndrome) protein translocation into the nucleus by a nuclear localization signal. Biochemical and biophysical research communications 54 9388480
2021 Functions of BLM Helicase in Cells: Is It Acting Like a Double-Edged Sword? Frontiers in genetics 53 33777104
2003 Heterozygosity for the BLM(Ash) mutation and cancer risk. Cancer research 51 12702560
2018 HERC2 Facilitates BLM and WRN Helicase Complex Interaction with RPA to Suppress G-Quadruplex DNA. Cancer research 50 30279242
2012 The human RecQ helicases BLM and RECQL4 cooperate to preserve genome stability. Nucleic acids research 50 22544709
2006 BLM is an early responder to DNA double-strand breaks. Biochemical and biophysical research communications 50 16876111
2013 TopBP1 controls BLM protein level to maintain genome stability. Molecular cell 49 24239288
2011 Fanconi anemia and Bloom's syndrome crosstalk through FANCJ-BLM helicase interaction. Trends in genetics : TIG 48 22024395
2010 Mechanisms of recombination between diverged sequences in wild-type and BLM-deficient mouse and human cells. Molecular and cellular biology 48 20154148
2011 BLM helicase facilitates RNA polymerase I-mediated ribosomal RNA transcription. Human molecular genetics 47 22106380
2007 BLM helicase-dependent and -independent roles of 53BP1 during replication stress-mediated homologous recombination. The Journal of cell biology 47 17591918
2004 Clinical features of Bloom syndrome and function of the causative gene, BLM helicase. Expert review of molecular diagnostics 46 15137905
2002 The BLM helicase is necessary for normal DNA double-strand break repair. Cancer research 45 12019152
2014 The role of post-translational modifications in fine-tuning BLM helicase function during DNA repair. DNA repair 44 25150915
2016 FANCD2 limits BLM-dependent telomere instability in the alternative lengthening of telomeres pathway. Human molecular genetics 41 27427384
2007 Cooperative roles of vertebrate Fbh1 and Blm DNA helicases in avoidance of crossovers during recombination initiated by replication fork collapse. Molecular and cellular biology 41 17283053
2020 Heterozygous germline BLM mutations increase susceptibility to asbestos and mesothelioma. Proceedings of the National Academy of Sciences of the United States of America 40 33318203
2012 The roles of WRN and BLM RecQ helicases in the Alternative Lengthening of Telomeres. Nucleic acids research 39 22989712
2009 Association between polymorphisms in RMI1, TOP3A, and BLM and risk of cancer, a case-control study. BMC cancer 34 19432957
2020 Human RPA activates BLM's bidirectional DNA unwinding from a nick. eLife 33 32101168
2019 Single-molecule visualization of human BLM helicase as it acts upon double- and single-stranded DNA substrates. Nucleic acids research 33 31544923
2014 Association of BLM and BRCA1 during Telomere Maintenance in ALT Cells. PloS one 33 25084169
2002 Characterization and potential function of a novel testis-specific nucleoporin BS-63. Molecular reproduction and development 33 11774384
2021 USP37 regulates DNA damage response through stabilizing and deubiquitinating BLM. Nucleic acids research 32 34606619
2019 Helicases FANCJ, RTEL1 and BLM Act on Guanine Quadruplex DNA in Vivo. Genes 32 31683575
2018 BLM prevents instability of structure-forming DNA sequences at common fragile sites. PLoS genetics 31 30496191
2015 The risk for developing cancer in Israeli ATM, BLM, and FANCC heterozygous mutation carriers. Cancer genetics 31 26778106
2014 RECQL5 and BLM exhibit divergent functions in cells defective for the Fanconi anemia pathway. Nucleic acids research 31 25520194
2012 Collaborating functions of BLM and DNA topoisomerase I in regulating human rDNA transcription. Mutation research 31 23261817
2019 PLK1 facilitates chromosome biorientation by suppressing centromere disintegration driven by BLM-mediated unwinding and spindle pulling. Nature communications 30 31253795
2015 Unwinding forward and sliding back: an intermittent unwinding mode of the BLM helicase. Nucleic acids research 30 25765643
2012 Multimeric BLM is dissociated upon ATP hydrolysis and functions as monomers in resolving DNA structures. Nucleic acids research 30 22885301
2009 BLM helicase stimulates the ATPase and chromatin-remodeling activities of RAD54. Journal of cell science 30 19671661
2008 The fission yeast BLM homolog Rqh1 promotes meiotic recombination. Genetics 30 18562672
2024 BLM helicase unwinds lagging strand substrates to assemble the ALT telomere damage response. Molecular cell 29 38593805
2020 Phosphorylation of the RecQ Helicase Sgs1/BLM Controls Its DNA Unwinding Activity during Meiosis and Mitosis. Developmental cell 28 32504558
2014 DNA helicase HIM-6/BLM both promotes MutSγ-dependent crossovers and antagonizes MutSγ-independent interhomolog associations during caenorhabditis elegans meiosis. Genetics 27 25053665
2020 Investigating the pathogenic SNPs in BLM helicase and their biological consequences by computational approach. Scientific reports 26 32704157
2017 RecQ helicase BLM regulates prostate cancer cell proliferation and apoptosis. Oncology letters 26 28943928
2018 BLM can regulate cataract progression by influencing cell vitality and apoptosis. Experimental eye research 25 30227115
2016 BLM promotes the activation of Fanconi Anemia signaling pathway. Oncotarget 25 27083049
2009 Genomic instability resulting from Blm deficiency compromises development, maintenance, and function of the B cell lineage. Journal of immunology (Baltimore, Md. : 1950) 25 19109166
2009 Genetic variation in the NBS1, MRE11, RAD50 and BLM genes and susceptibility to non-Hodgkin lymphoma. BMC medical genetics 25 19917125
2017 Structural Insight into BLM Recognition by TopBP1. Structure (London, England : 1993) 24 28919440
2015 Mre11 and Blm-Dependent Formation of ALT-Like Telomeres in Ku-Deficient Ustilago maydis. PLoS genetics 24 26492073
2023 BLM helicase protein negatively regulates stress granule formation through unwinding RNA G-quadruplex structures. Nucleic acids research 23 37503837
2020 Structural and biochemical studies of the glycosyltransferase Bs-YjiC from Bacillus subtilis. International journal of biological macromolecules 23 33152360
2011 Chromosome breakage is regulated by the interaction of the BLM helicase and topoisomerase IIalpha. Cancer research 23 21224348
2025 Irinotecan alleviates chemoresistance to anthracyclines through the inhibition of AARS1-mediated BLM lactylation and homologous recombination repair. Signal transduction and targeted therapy 22 40634292
2021 Ellagic Acid Attenuates BLM-Induced Pulmonary Fibrosis via Inhibiting Wnt Signaling Pathway. Frontiers in pharmacology 22 33912053
2001 Selective cleavage of BLM, the bloom syndrome protein, during apoptotic cell death. The Journal of biological chemistry 22 11154689
2023 Fraxetin alleviates BLM-induced idiopathic pulmonary fibrosis by inhibiting NCOA4-mediated epithelial cell ferroptosis. Inflammation research : official journal of the European Histamine Research Society ... [et al.] 21 37798541
2020 BLM has Contrary Effects on Repeat-Mediated Deletions, based on the Distance of DNA DSBs to a Repeat and Repeat Divergence. Cell reports 21 32023454