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Showing TOP3A — TOP3 is a alias.

TOP3A

DNA topoisomerase 3-alpha · UniProt Q13472

Length
1001 aa
Mass
112.4 kDa
Annotated
2026-06-10
54 papers in source corpus 27 papers cited in narrative 26 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 7/7 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

TOP3A encodes a single-strand-specific type IA DNA topoisomerase that resolves recombination and replication intermediates to preserve genome stability, acting predominantly as the catalytic subunit of the conserved RecQ-helicase complex (Sgs1/BLM-Top3/TOP3A-Rmi1, the STR/BTR complex) (PMID:1324925, PMID:7969174, PMID:15899853). The enzyme relaxes negatively supercoiled DNA, prefers single-stranded substrates, and operates through a covalent 5'-phosphotyrosyl protein-DNA intermediate at its active-site tyrosine (Tyr-356 in yeast), whose catalytic activity is required for repair of DNA damage and for normal S-phase progression (PMID:1324925, PMID:12036100, PMID:16899506). Within the STR/BTR complex it migrates and decatenates double Holliday junctions to yield exclusively non-crossover products (dissolution), with the helicase providing strand unwinding, Top3 performing strand passage, and Rmi1 stabilizing the open Top3-DNA covalent intermediate to stimulate the final decatenation step (PMID:20935631, PMID:22885009); the complex also disrupts D-loops in a catalysis-dependent manner and stimulates DNA end resection by enhancing helicase unwinding (PMID:25699708, PMID:20811461). Beyond junction dissolution, TOP3A cooperates with the PICH helicase to generate positive DNA supercoiling that facilitates sister-chromatid disjunction (PMID:30936532), and Top3-Rmi1 has a helicase-independent late role in resolving recombination-dependent entanglements for anaphase segregation (PMID:25699709, PMID:25699707). Its activity is regulated by Smc5/6-dependent sumoylation that promotes inter-subunit interactions and accumulation at repair centers, and by Smc5/6-mediated retention at replication-pausing sites (PMID:27373152, PMID:33833229). A distinct mitochondrial isoform is matured by mitochondrial processing peptidase cleavage of ~90 C-terminal residues, which enhances ssDNA binding and decatenation and uncouples it from BTRR interactions, enabling autonomous mtDNA maintenance (PMID:41189053). Biallelic TOP3A mutations reduce protein levels and cause elevated sister chromatid exchanges, chromosome segregation defects, and genome instability, producing either a Bloom syndrome-like nuclear disorder or adult-onset mitochondrial disease depending on the severity of the catalytic defect (PMID:30057030, PMID:37013609).

Mechanistic history

Synthesis pass · year-by-year structured walk · 25 steps
  1. 1992 High

    Established the fundamental enzymatic identity of the TOP3 product, defining it as a single-strand-specific type IA topoisomerase rather than a conventional supercoil relaxase.

    Evidence Protein purification and in vitro topoisomerase assays with covalent protein-DNA complex mapping in yeast

    PMID:1324925

    Open questions at the time
    • Cellular substrates and pathway context unknown
    • No partner proteins identified at this stage
  2. 1994 High

    Placed Top3 in a functional pathway by identifying the RecQ helicase Sgs1 as a physical and genetic partner, framing the topoisomerase as part of a helicase-coupled genome-stability module.

    Evidence Two-hybrid screen and genetic suppressor/epistasis analysis in yeast

    PMID:7969174

    Open questions at the time
    • Biochemical mechanism of the Sgs1-Top3 partnership not defined
    • Substrate processed by the pair unknown
  3. 1996 High

    Demonstrated that the human TOP3A ortholog is a functional supercoil-reducing topoisomerase, extending the yeast biology to humans.

    Evidence cDNA cloning, heterologous yeast expression, topoisomerase activity assay, FISH mapping

    PMID:8622991

    Open questions at the time
    • Human complex partners not yet established
    • In vivo function in human cells uncharacterized
  4. 2001 Medium

    Mapped the molecular interface of the helicase-topoisomerase interaction to the Sgs1 N-terminus, linking complex assembly to DNA repair function.

    Evidence Deletion/missense mutagenesis with two-hybrid and DNA damage sensitivity assays

    PMID:11523801

    Open questions at the time
    • Structural basis of binding not resolved
    • Mapped on Sgs1 side, not Top3 side
  5. 2002 Medium

    Showed that Top3 catalytic activity has an Sgs1-independent role in DNA damage repair, separating the topoisomerase's enzymatic contribution from helicase association.

    Evidence Active-site Y356F mutagenesis, DNA damage sensitivity, and epistasis analysis in yeast

    PMID:12036100

    Open questions at the time
    • Specific intermediate processed independently of Sgs1 not identified
    • Single lab
  6. 2003 High

    Defined the cellular outcome of the Sgs1-Top3 pathway as crossover suppression during double-strand break repair via removal of double Holliday junctions.

    Evidence Genetic epistasis and physical monitoring of recombination intermediates in mitotic yeast

    PMID:14622595

    Open questions at the time
    • Direct biochemical demonstration of dHJ resolution not yet shown
    • Role of additional subunits unaddressed
  7. 2005 High

    Identified Rmi1 as the third subunit and a structure-specific DNA-binding component, establishing the heterotrimeric STR architecture.

    Evidence Co-IP, recombinant interaction, DNA binding assay, and genetic epistasis in yeast

    PMID:15899853

    Open questions at the time
    • Mechanistic contribution of Rmi1 to catalysis not yet defined
  8. 2010 High

    Reconstituted dissolution from purified components, proving Sgs1-Top3 alone migrate and disentangle a dHJ to give exclusively non-crossovers and assigning Rmi1 a decatenation-stimulating role.

    Evidence In vitro reconstitution with purified proteins and dHJ dissolution assay

    PMID:20935631

    Open questions at the time
    • Stoichiometry and dynamics in vivo not addressed
    • Regulation of the reaction unknown
  9. 2010 High

    Revealed a second activity of the complex in DNA end resection, where Top3-Rmi1 stimulates Sgs1 unwinding and aids recruitment of the resection machinery.

    Evidence Full in vitro reconstitution of resection with purified Dna2, Sgs1, RPA, Top3-Rmi1, MRX

    PMID:20811461

    Open questions at the time
    • In vivo contribution relative to other resection nucleases not quantified
  10. 2012 High

    Dissected the strand-passage decatenation mechanism, assigning sequential roles to each subunit including RPA stimulation and Rmi1 stabilization of the open Top3-DNA intermediate.

    Evidence In vitro reconstitution and catenation/decatenation assays with purified proteins

    PMID:22885009

    Open questions at the time
    • Structural snapshots of the open intermediate not provided
  11. 2013 High

    Refined the assembly interface using NMR, showing a transient α-helix in the disordered Sgs1 N-terminus mediates Top3/Rmi1 binding and is required for genome stability.

    Evidence NMR, in vitro binding, proline mutagenesis, and in vivo genome stability assays

    PMID:24038467

    Open questions at the time
    • Full complex structure not resolved
  12. 2013 Medium

    Distinguished substrate-specific activities, showing Top3 alone can resolve hemicatenane-like Rec-X intermediates but requires the helicase for dHJ processing.

    Evidence In vitro assays with purified Top3 on synthetic substrates plus 2D gels and genetics

    PMID:24100144

    Open questions at the time
    • In vivo prevalence of Rec-X substrates uncertain
    • Single lab
  13. 2015 High

    Demonstrated catalysis-dependent D-loop disruption by Top3 and the human TOP3A-RMI1-RMI2 complex, broadening the complex's anti-recombinogenic repertoire.

    Evidence In vitro D-loop dissolution assays with purified yeast and human proteins and catalytic mutants

    PMID:25699708

    Open questions at the time
    • Why disruption is specific to Rad51/Rad54-mediated D-loops mechanistically unexplained
  14. 2015 High

    Established that Top3-Rmi1 strand-passage activity underlies all Sgs1 meiotic functions and revealed a separate Sgs1-independent role in resolving entanglements for anaphase segregation.

    Evidence Meiotic genetics, catalytic mutants, joint-molecule monitoring, and segregation assays (concordant multi-lab)

    PMID:25699707 PMID:25699709

    Open questions at the time
    • Molecular nature of the late segregation substrate not defined
  15. 2016 Medium

    Identified Smc5/6-dependent sumoylation as a regulatory layer promoting STR subunit interactions and accumulation at repair centers.

    Evidence Co-IP, sumoylation assays, genetics, and live-cell imaging of repair foci

    PMID:27373152

    Open questions at the time
    • Specific sumoylated residues and their individual effects not fully mapped
    • Single lab
  16. 2018 Medium

    Linked human TOP3A loss-of-function to disease, showing biallelic mutations reduce protein levels and cause SCE elevation, segregation defects, and mitochondrial dysfunction.

    Evidence Patient-derived cells with SCE, Western blot, and segregation analysis

    PMID:30057030

    Open questions at the time
    • Genotype-phenotype relationship across variant severity not yet resolved
    • Single study
  17. 2019 High

    Uncovered a reverse-gyrase-like activity in which PICH and TOP3A together generate positive supercoiling proposed to aid sister-chromatid disjunction.

    Evidence Single-molecule manipulation and in vitro reconstitution with purified PICH and TOP3A

    PMID:30936532

    Open questions at the time
    • In vivo requirement for this activity not demonstrated
  18. 2019 Medium

    Connected the BTR complex to telomere maintenance, showing FANCM restrains ALT through its interaction with BLM-TOP3A-RMI.

    Evidence siRNA depletion, ALT biomarker and break-induced synthesis assays, Co-IP

    PMID:31138797

    Open questions at the time
    • Direct enzymatic role of TOP3A at ALT telomeres not isolated
    • Single lab
  19. 2021 Medium

    Showed Smc5/6 spatially regulates Top3 by promoting its retention at natural pausing sites where it processes joint molecules at replication termination.

    Evidence ChIP co-localization, depletion, 2D gels, and suppressor isolation in yeast

    PMID:33833229

    Open questions at the time
    • Mechanism of Smc5/6-mediated retention unresolved
    • Single lab
  20. 2022 Medium

    Established TOP3A as a driver of the ALT phenotype in cancer cells, required for BLM localization and ALT DNA synthesis and countering ATRX-mediated inhibition.

    Evidence Overexpression/knockdown in ALT cell lines with BLM imaging and ALT synthesis assays

    PMID:35920001

    Open questions at the time
    • Whether TOP3A catalytic activity is required for ALT not separated from scaffolding
    • Single lab
  21. 2023 Medium

    Defined the dual nuclear/mitochondrial localization and a severity-dependent disease spectrum, with milder catalytic defects selectively impairing mtDNA maintenance.

    Evidence Patient cells with mtDNA maintenance assays, enzyme activity, and fractionation

    PMID:37013609

    Open questions at the time
    • Quantitative catalytic thresholds for each clinical outcome not established
    • Single study
  22. 2024 Low

    Detailed TOP3A telomere functions in ALT cells, including TERF2 stabilization and TERRA/ssTeloC promotion, with DNA-protein crosslinks reversing these effects.

    Evidence Telomere ChIP, protein stability, TERRA and ssTeloC assays, crosslink induction (preprint)

    PMID:39803571

    Open questions at the time
    • Preprint, not peer-reviewed
    • Single lab
    • Direct catalytic mechanism on telomeric substrates not reconstituted
  23. 2024 Low

    Mapped genome-wide TOP3A occupancy to promoters and 5'-regions of transcribed genes, implicating it in transcription-replication conflict sites.

    Evidence CUT&Tag binding mapping with replication inhibition (preprint)

    PMID:38948815

    Open questions at the time
    • Preprint, not peer-reviewed
    • No functional validation of TRC resolution
    • Binding does not establish activity
  24. 2025 High

    Explained how the mitochondrial isoform is functionally specialized, showing mitochondrial processing peptidase cleavage enhances ssDNA binding and decatenation and uncouples it from the nuclear BTRR complex.

    Evidence Cleavage identification, MPP assay, in vitro ssDNA binding/decatenation, mass spectrometry, fractionation

    PMID:41189053

    Open questions at the time
    • In vivo regulation of cleavage timing not addressed
  25. 2025 Medium

    Added RAD54L2 as a regulator of the BTR complex, promoting BLM chromatin recruitment and suppressing SCEs via its ATPase domain.

    Evidence BioID proximity proteomics, Co-IP, SCE assay, chromatin fractionation

    PMID:39870965

    Open questions at the time
    • Interaction is with BLM rather than TOP3A directly
    • Single lab

Open questions

Synthesis pass · forward-looking unresolved questions
  • How TOP3A activity is partitioned and regulated between its dissolution, resection-stimulating, supercoiling, telomeric ALT, and transcription-replication conflict roles in human cells remains unresolved.
  • No structure of the human BTRR complex on substrate
  • Catalytic requirement for ALT function not separated from scaffolding
  • TRC resolution role rests only on binding maps

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140097 catalytic activity, acting on DNA 3 GO:0003677 DNA binding 2 GO:0016853 isomerase activity 2 GO:0016787 hydrolase activity 1
Localization
GO:0005694 chromosome 2 GO:0005739 mitochondrion 2 GO:0005634 nucleus 1
Pathway
R-HSA-73894 DNA Repair 3 R-HSA-1640170 Cell Cycle 2 R-HSA-1474165 Reproduction 1 R-HSA-69306 DNA Replication 1
Partners
BLMFANCMPICHRMI1RMI2SGS1SMC5
Complex memberships
BLM-TOP3A-RMI1-RMI2 (BTR/BTRR)Sgs1-Top3-Rmi1 (STR)

Evidence

Reading pass · 26 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1992 Yeast TOP3 gene product (74-kDa protein) was purified and shown to be a single-strand-specific type IA DNA topoisomerase that partially relaxes negatively but not positively supercoiled DNA, forms a covalent protein-DNA complex linked to the 5' DNA phosphoryl group, and has strong preference for single-stranded DNA substrates. Protein purification, in vitro topoisomerase assay, protein-DNA covalent complex identification, sequencing of cleavage sites The Journal of biological chemistry High 1324925
1994 Yeast Top3 physically interacts with the RecQ helicase homolog Sgs1; Sgs1 was identified in a two-hybrid screen for Top3-interacting proteins, and mutations in SGS1 suppress both the growth defect and increased genomic instability of top3 mutants, placing Sgs1 and Top3 in the same pathway. Two-hybrid screen (protein interaction), genetic epistasis/suppressor analysis Molecular and cellular biology High 7969174
1996 Human TOP3A (TOP3) encodes a DNA topoisomerase III that reduces supercoils in negatively supercoiled DNA; expression of the human cDNA in yeast top1 cells lacking endogenous topoisomerase I yielded supercoil-reducing activity in cell extracts. The gene is located at chromosome 17p11.2-12. cDNA cloning, heterologous expression in yeast, in vitro topoisomerase activity assay, FISH chromosomal mapping Proceedings of the National Academy of Sciences of the United States of America High 8622991
2001 The N-terminal 45 amino acids of Sgs1 (specifically residues 4–13) are required for interaction with Top3; missense mutations in this region abolish Top3 binding and abolish complementation of MMS sensitivity and suppression of hyper-recombination in sgs1 mutants. Deletion and missense mutagenesis, two-hybrid interaction assay, DNA damage sensitivity assay Molecular genetics and genomics : MGG Medium 11523801
2002 Top3 DNA topoisomerase catalytic activity (requiring the active-site Tyr-356) is required to repair MMS-induced DNA damage independently of Sgs1; a catalytic-dead TOP3(Y356F) allele fails to restore MMS sensitivity of sgs1-top3 double mutants to sgs1 single mutant levels, and TOP3 is epistatic to RAD52. Active-site mutagenesis (Y356F), DNA damage sensitivity assay, epistasis analysis Genes & genetic systems Medium 12036100
2003 Sgs1 and its associated topoisomerase Top3 suppress crossovers during double-strand break repair by removing double Holliday junction intermediates from a crossover-producing repair pathway in mitotic yeast cells. Genetic epistasis analysis, physical monitoring of recombination intermediates, deletion of SGS1/SRS2 Cell High 14622595
2005 Rmi1 forms a heteromeric complex with Sgs1-Top3 in yeast; Rmi1 interacts directly with Top3 in a recombinant system; loss of either Rmi1 or Top3 compromises the partner's interaction with Sgs1; Rmi1 is a structure-specific DNA binding protein with preference for cruciform structures. Co-immunoprecipitation, recombinant protein interaction assay, DNA binding assay, genetic epistasis Molecular and cellular biology High 15899853
2006 The catalytic (decatenation) activity of Top3 (Tyr-356 residue) is not required for DNA damage checkpoint activation but is required for normal S-phase progression after DNA damage; overexpression of catalytic-dead TOP3(Y356F) causes persistence of X-shaped DNA molecules after MMS exposure. Dominant-negative allele overexpression (TOP3-Y356F), 2D gel electrophoresis of DNA intermediates, checkpoint assays, caffeine override experiment Molecular biology of the cell Medium 16899506
2010 Sgs1 and Top3 proteins together are sufficient to migrate and disentangle a double Holliday junction (dHJ) to produce exclusively non-crossover recombination products (dissolution); Rmi1 stimulates dHJ dissolution by stimulating DNA decatenation (removing last strand linkages) rather than affecting initial HJ migration rate. In vitro biochemical reconstitution with purified proteins, dHJ dissolution assay Nature structural & molecular biology High 20935631
2010 Top3-Rmi1 heterodimer stimulates DNA end resection by forming a complex with Sgs1, which unexpectedly stimulates Sgs1 DNA unwinding activity; Top3-Rmi1 and MRX are important for recruitment of the Sgs1-Dna2 complex to DSBs. Biochemical reconstitution of DNA end resection in vitro with purified Dna2, Sgs1, RPA, Top3-Rmi1, MRX Nature High 20811461
2012 Sgs1, Top3, Rmi1, and RPA coordinate dsDNA decatenation through sequential passage of single strands; Sgs1 is required for dsDNA unwinding and has a structural role in strand passage; RPA stimulates Sgs1 unwinding and Top3 strand passage; Rmi1 stabilizes the open Top3-DNA covalent complex intermediate and slows DNA relaxation but stimulates decatenation. In vitro biochemical reconstitution with purified proteins, catenation/decatenation assays, mechanistic dissection of individual subunit roles Molecular cell High 22885009
2013 The N-terminal 125 residues of Sgs1 are disordered and contain a transient α-helix (residues 25–38) critical for binding Top3 and Rmi1; proline substitutions disrupting this helix impair Top3/Rmi1 binding in vitro and cause hypersensitivity to DNA damaging agents and increased genome rearrangements in vivo. NMR spectroscopy, in vitro binding assays, proline mutagenesis, DNA damage sensitivity assays, genome stability assays Nucleic acids research High 24038467
2013 Top3 alone (unassisted by Sgs1 and Rmi1) can resolve hemicatenane-related template switch recombination intermediates (Rec-X structures) but not double Holliday junction intermediates; purified Top3 resolves a synthetic Rec-X but not a synthetic dHJ in vitro. In vitro assay with purified Top3, synthetic Rec-X and dHJ substrates, 2D gel electrophoresis of genomic DNA, genetic experiments The Journal of biological chemistry Medium 24100144
2015 Top3 disrupts D loops (displacement loops formed during homologous recombination) through a mechanism that depends on Top3's catalytic activity; Top3 specifically disrupts D loops mediated by yeast Rad51/Rad54 but not protein-free D loops or those mediated by bacterial RecA or human RAD51/RAD54; the human Topoisomerase IIIα-RMI1-RMI2 complex also dissolves D loops. In vitro D-loop dissolution assay with purified proteins, catalytic mutant analysis Molecular cell High 25699708
2015 Top3-Rmi1 strand-passage (decatenase) activity is required for all known Sgs1 functions in meiotic recombination, including channeling joint molecules into crossover and noncrossover pathways and suppressing non-allelic recombination; additionally, Top3-Rmi1 has a distinct Sgs1-independent late function in resolving recombination-dependent chromosome entanglements to allow anaphase segregation. Genetic analysis in yeast meiosis, catalytic mutant analysis, physical monitoring of joint molecule intermediates, chromosome segregation assays Molecular cell High 25699707 25699709
2016 Sgs1, Top3, and Rmi1 are sumoylated by the Smc5/6 SUMO E3 complex upon generation of recombination structures; sumoylation promotes STR inter-subunit interactions and accumulation at DNA repair centers; reduced STR sumoylation leads to accumulation of recombination intermediates. Co-immunoprecipitation, sumoylation assays, genetic analysis, live-cell imaging of repair foci Cell reports Medium 27373152
2018 Biallelic mutations in TOP3A substantially reduce cellular levels of TopIIIα (the human TOP3A protein), leading to elevated sister chromatid exchanges (SCEs), chromosome segregation defects, and genome instability consistent with impaired dissolution of DNA recombination/replication intermediates; clinical features of mitochondrial dysfunction are also evident, consistent with a mitochondrial DNA decatenation function of TopIIIα. Patient-derived cell lines with biallelic TOP3A mutations, SCE assay, Western blot (protein levels), chromosome segregation analysis American journal of human genetics Medium 30057030
2019 Human PICH helicase and Topoisomerase 3α (TOP3A) combine to create high-density positive DNA supercoiling in vitro, analogous to a reverse-gyrase activity; PICH progressively extrudes hypernegatively supercoiled DNA loops that are relaxed by TOP3A, generating positive supercoiling proposed to facilitate sister-chromatid disjunction by Topoisomerase 2α. Single-molecule manipulation, in vitro biochemical reconstitution of supercoiling activity with purified PICH and TOP3A Nature structural & molecular biology High 30936532
2019 FANCM depletion provokes ALT (alternative lengthening of telomeres) activity; FANCM-mediated attenuation of ALT requires its interaction with the BLM-TOP3A-RMI (BTR) complex but not the FA core complex, indicating that FANCM functions with the BTR complex to restrain ALT replication stress at telomeres. siRNA depletion, ALT biomarker assays, break-induced telomere synthesis assays, co-immunoprecipitation Nature communications Medium 31138797
2021 Smc5/6 co-localizes with Sgs1-Top3-Rmi1 (STR) at natural pausing sites (NPSs) on chromosomes, facilitates Top3 retention at these sites, and individual depletions of STR subunits and Smc5/6 cause similar accumulation of joint molecules (reversed forks, double Holliday junctions, hemicatenanes), indicating Smc5/6 regulates Top3 DNA processing activities at replication termination sites. ChIP co-localization, genetic depletion, 2D gel electrophoresis of DNA intermediates, intra-allelic suppressor isolation Nature communications Medium 33833229
2022 TOP3A overexpression in ALT cancer cells counters ATRX-mediated ALT inhibition; TOP3A knockdown disrupts the ALT phenotype in ATRX-wt cells; TOP3A is required for proper BLM localization and promotes ALT DNA synthesis. TOP3A overexpression and knockdown in ALT cancer cell lines, BLM localization imaging, ALT DNA synthesis assay, functional genomics EMBO molecular medicine Medium 35920001
2023 TOP3A localizes to both the nucleus and mitochondria via two distinct isoforms; pathogenic TOP3A variants cause either a Bloom syndrome-like nuclear disorder or adult-onset mitochondrial disease depending on overall severity of the catalytic defect, with milder variants selectively impairing mitochondrial DNA maintenance. Patient cell lines with biallelic TOP3A variants, mtDNA maintenance assays, enzyme activity characterization, cellular fractionation/localization EMBO molecular medicine Medium 37013609
2024 TOP3A is enriched at telomeres of ALT cancer cells (but not telomerase-positive cells), stabilizes the shelterin protein TERF2 in ALT cells, promotes enrichment of long non-coding TERRA at telomeres, and promotes generation of single-stranded telomeric C-strand (ssTeloC) DNA; TOP3A-DNA-protein crosslinks suppress TERRA enrichment and destabilize TERF2. ChIP/telomere enrichment assays, protein stability assays, TERRA assay, ssTeloC detection, TOP3A-DNA crosslink induction bioRxivpreprint Low 39803571
2024 Genome-wide mapping shows TOP3A binding is concentrated at promoters and 5'-regions of transcribed genes and is suppressed by DNA replication inhibition, suggesting TOP3A is recruited to sites of transcription-replication conflicts (TRCs). CUT&Tag genome-wide topoisomerase binding mapping, replication inhibition experiment bioRxivpreprint Low 38948815
2025 The mitochondrial isoform of TOP3A undergoes proteolytic cleavage by the mitochondrial processing peptidase, removing ~90 amino acids from the C-terminus; this cleavage enhances single-stranded DNA binding and decatenation activity, and uncouples the mitochondrial isoform from nuclear BTRR complex protein interactions, enabling autonomous function in mtDNA maintenance. Protein biochemistry (cleavage identification), mitochondrial processing peptidase assay, in vitro ssDNA binding and decatenation activity assays, mass spectrometry, subcellular fractionation Nucleic acids research High 41189053
2025 RAD54L2 physically interacts with BLM (component of the BLM-TOP3A-RMI1-RMI2/BTRR complex) and suppresses sister chromatid exchanges; RAD54L2 is important for recruitment of BLM to chromatin and requires an intact ATPase domain to promote non-crossover recombination. Proximity proteomics (BioID), co-immunoprecipitation, SCE assay, chromatin fractionation EMBO reports Medium 39870965

Source papers

Stage 0 corpus · 54 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1994 The yeast type I topoisomerase Top3 interacts with Sgs1, a DNA helicase homolog: a potential eukaryotic reverse gyrase. Molecular and cellular biology 599 7969174
2003 Srs2 and Sgs1-Top3 suppress crossovers during double-strand break repair in yeast. Cell 483 14622595
2010 DNA end resection by Dna2-Sgs1-RPA and its stimulation by Top3-Rmi1 and Mre11-Rad50-Xrs2. Nature 383 20811461
2002 Alternate pathways involving Sgs1/Top3, Mus81/ Mms4, and Srs2 prevent formation of toxic recombination intermediates from single-stranded gaps created by DNA replication. Proceedings of the National Academy of Sciences of the United States of America 274 12475932
2001 Functional overlap between Sgs1-Top3 and the Mms4-Mus81 endonuclease. Genes & development 268 11641278
2003 Slx1-Slx4 is a second structure-specific endonuclease functionally redundant with Sgs1-Top3. Genes & development 174 12832395
2019 The FANCM-BLM-TOP3A-RMI complex suppresses alternative lengthening of telomeres (ALT). Nature communications 164 31138797
2010 Rmi1 stimulates decatenation of double Holliday junctions during dissolution by Sgs1-Top3. Nature structural & molecular biology 162 20935631
2005 Yeast Rmi1/Nce4 controls genome stability as a subunit of the Sgs1-Top3 complex. Molecular and cellular biology 134 15899853
1996 Human TOP3: a single-copy gene encoding DNA topoisomerase III. Proceedings of the National Academy of Sciences of the United States of America 123 8622991
1992 Identification of the yeast TOP3 gene product as a single strand-specific DNA topoisomerase. The Journal of biological chemistry 111 1324925
2015 Top3-Rmi1 dissolve Rad51-mediated D loops by a topoisomerase-based mechanism. Molecular cell 103 25699708
2015 Pervasive and essential roles of the Top3-Rmi1 decatenase orchestrate recombination and facilitate chromosome segregation in meiosis. Molecular cell 90 25699709
2015 Top3-Rmi1 DNA single-strand decatenase is integral to the formation and resolution of meiotic recombination intermediates. Molecular cell 89 25699707
2012 Decatenation of DNA by the S. cerevisiae Sgs1-Top3-Rmi1 and RPA complex: a mechanism for disentangling chromosomes. Molecular cell 84 22885009
2007 Shu proteins promote the formation of homologous recombination intermediates that are processed by Sgs1-Rmi1-Top3. Molecular biology of the cell 84 17671161
2005 A genetic screen for top3 suppressors in Saccharomyces cerevisiae identifies SHU1, SHU2, PSY3 and CSM2: four genes involved in error-free DNA repair. Genetics 83 15654096
2002 Mutations in homologous recombination genes rescue top3 slow growth in Saccharomyces cerevisiae. Genetics 81 12399378
2016 Smc5/6 Mediated Sumoylation of the Sgs1-Top3-Rmi1 Complex Promotes Removal of Recombination Intermediates. Cell reports 72 27373152
1999 The top3(+) gene is essential in Schizosaccharomyces pombe and the lethality associated with its loss is caused by Rad12 helicase activity. Nucleic acids research 67 10572171
2018 Mutations in TOP3A Cause a Bloom Syndrome-like Disorder. American journal of human genetics 64 30057030
2004 Multiple genetic pathways involving the Caenorhabditis elegans Bloom's syndrome genes him-6, rad-51, and top-3 are needed to maintain genome stability in the germ line. Molecular and cellular biology 63 15143192
2001 The N-terminal region of Sgs1, which interacts with Top3, is required for complementation of MMS sensitivity and suppression of hyper-recombination in sgs1 disruptants. Molecular genetics and genomics : MGG 50 11523801
1992 Genome rearrangement in top3 mutants of Saccharomyces cerevisiae requires a functional RAD1 excision repair gene. Molecular and cellular biology 49 1328869
2011 Holliday junction-containing DNA structures persist in cells lacking Sgs1 or Top3 following exposure to DNA damage. Proceedings of the National Academy of Sciences of the United States of America 47 21383164
2006 The absence of Top3 reveals an interaction between the Sgs1 and Pif1 DNA helicases in Saccharomyces cerevisiae. Genetics 40 16816432
2019 PICH and TOP3A cooperate to induce positive DNA supercoiling. Nature structural & molecular biology 37 30936532
2006 Top3 processes recombination intermediates and modulates checkpoint activity after DNA damage. Molecular biology of the cell 37 16899506
2000 Genetic analysis of the Saccharomyces cerevisiae Sgs1 helicase defines an essential function for the Sgs1-Top3 complex in the absence of SRS2 or TOP1. Molecular & general genetics : MGG 37 11016837
2022 TOP3A amplification and ATRX inactivation are mutually exclusive events in pediatric osteosarcomas using ALT. EMBO molecular medicine 34 35920001
2009 Association between polymorphisms in RMI1, TOP3A, and BLM and risk of cancer, a case-control study. BMC cancer 34 19432957
2002 Supercomplex formation between Mlh1-Mlh3 and Sgs1-Top3 heterocomplexes in meiotic yeast cells. Biochemical and biophysical research communications 28 12200140
2023 Pathological variants in TOP3A cause distinct disorders of mitochondrial and nuclear genome stability. EMBO molecular medicine 25 37013609
2002 Functional and physical interaction between Sgs1 and Top3 and Sgs1-independent function of Top3 in DNA recombination repair. Genes & genetic systems 24 12036100
2004 Requirement for Schizosaccharomyces pombe Top3 in the maintenance of chromosome integrity. Journal of cell science 21 15340008
2013 A transient α-helical molecular recognition element in the disordered N-terminus of the Sgs1 helicase is critical for chromosome stability and binding of Top3/Rmi1. Nucleic acids research 20 24038467
2008 The genetic consequences of ablating helicase activity and the Top3 interaction domain of Sgs1. DNA repair 20 18272435
2021 Smc5/6 functions with Sgs1-Top3-Rmi1 to complete chromosome replication at natural pause sites. Nature communications 19 33833229
2016 Hypoxia-inducible factor-targeting prodrug TOP3 combined with gemcitabine or TS-1 improves pancreatic cancer survival in an orthotopic model. Cancer science 18 27270607
2021 Predominant cellular mitochondrial dysfunction in the TOP3A gene-caused Bloom syndrome-like disorder. Biochimica et biophysica acta. Molecular basis of disease 16 33631320
2022 Novel TOP3A Variant Associated With Mitochondrial Disease: Expanding the Clinical Spectrum of Topoisomerase III Alpha-Related Diseases. Neurology. Genetics 15 35812164
2015 Top2 and Sgs1-Top3 Act Redundantly to Ensure rDNA Replication Termination. PLoS genetics 12 26630413
2009 WRN helicase defective in the premature aging disorder Werner syndrome genetically interacts with topoisomerase 3 and restores the top3 slow growth phenotype of sgs1 top3. Aging 12 20157511
2022 Chronic progressive external ophthalmoplegia plus syndrome due to homozygous missense variant in TOP3A gene. Clinical genetics 10 36544354
2007 Rmi1, a member of the Sgs1-Top3 complex in budding yeast, contributes to sister chromatid cohesion. EMBO reports 10 17571075
2013 Resolution by unassisted Top3 points to template switch recombination intermediates during DNA replication. The Journal of biological chemistry 8 24100144
2024 TOP3A coupling with replication forks and repair of TOP3A cleavage complexes. Cell cycle (Georgetown, Tex.) 6 38341866
2024 Genome-wide Mapping of Topoisomerase Binding Sites Suggests Topoisomerase 3α (TOP3A) as a Reader of Transcription-Replication Conflicts (TRC). bioRxiv : the preprint server for biology 5 38948815
2023 Identification of MKNK1 and TOP3A as ovarian endometriosis risk-associated genes using integrative genomic analyses and functional experiments. Computational and structural biotechnology journal 4 36851918
2024 Topoisomerase 3α (TOP3A) Dependent Alternative Lengthening of Telomeres (ALT). bioRxiv : the preprint server for biology 3 39803571
2019 Deletion of ULS1 confers damage tolerance in sgs1 mutants through a Top3-dependent D-loop mediated fork restart pathway. DNA repair 3 31005681
2025 The BLM-TOP3A-RMI1-RMI2 proximity map reveals that RAD54L2 suppresses sister chromatid exchanges. EMBO reports 2 39870965
2026 Identification of a TOP3A genetic variant as a novel biomarker for sensitivity to doxorubicin. Frontiers in pharmacology 0 42212268
2025 Proteolytic cleavage activates the mitochondrial isoform of TOP3A. Nucleic acids research 0 41189053

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