Affinage

SWI5

DNA repair protein SWI5 homolog · UniProt Q1ZZU3

Length
235 aa
Mass
26.7 kDa
Annotated
2026-06-10
61 papers in source corpus 44 papers cited in narrative 41 extracted findings
Cross-family judge vs UniProt: tie faithfulness: 7/7 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

The SWI5 symbol resolves to two mechanistically distinct, organism-dependent proteins within this corpus. In budding yeast, Swi5 is a C2H2 zinc-finger transcriptional activator that drives a wave of late-mitotic/early-G1 gene expression, including HO, SIC1, EGT2, and the Pho85 cyclins PCL9/PCL2 (PMID:1730413, PMID:8816483, PMID:9017392, PMID:8668141, PMID:9529390). Its DNA-binding zinc fingers are structurally independent modules in which finger 1 carries an N-terminal beta-strand extension that augments the canonical fold and DNA affinity (PMID:1453468, PMID:1453467, PMID:8736557), while promoter specificity (e.g. for HO) is encoded in a separate region that mediates cooperative DNA binding with the homeodomain protein Pho2/Grf10 (PMID:8355698, PMID:7902583, PMID:9774660, PMID:10409653). Once nuclear, Swi5 recruits the Mediator complex via its Gal11 module, with Swi/Snf required for Mediator binding, to activate transcription ahead of Pol II (PMID:11562354). Swi5 activity is tightly gated by the cell cycle: CDC28/Cdk1 phosphorylates serines in its NLS to enforce cytoplasmic retention until anaphase (PMID:1652372), Msn5 controls its nuclear export and synthesis (PMID:22374135), and SCF(Cdc4)-mediated ubiquitination degrades it in early G1 to terminate SIC1 transcription and permit S-phase entry (PMID:8449406, PMID:18787112). Separately, the small fission-yeast/mammalian Swi5 polypeptide (orthologous to budding-yeast Sae3 of the Mei5-Sae3 complex) forms a 1:1 heterodimer with Sfr1 that functions as a Rad51/Dmc1 recombination mediator and activator in homologous recombination (PMID:14663140, PMID:15466419, PMID:20976249, PMID:22033972). Crystallographic and biophysical work shows the complex adopts an elongated, sharply kinked crescent-shaped coiled-coil that docks within the Rad51 filament groove, with the Sfr1 N-terminus providing the recombinase interface (PMID:22033972, PMID:22405003, PMID:32204793). Functionally, Swi5-Sfr1 stabilizes the presynaptic filament by reducing recombinase dissociation, enhances ADP release to maintain the ATP-bound active filament state, overcomes RPA-imposed inhibition to load Dmc1 onto ssDNA, and stimulates strand exchange — activities conserved from fission yeast to mammals and regulated by phosphorylation of the intrinsically disordered Sfr1 subunit (PMID:16921379, PMID:19270307, PMID:22492707, PMID:24078249, PMID:30297419, PMID:37330173).

Mechanistic history

Synthesis pass · year-by-year structured walk · 21 steps
  1. 1991 High

    Established how Swi5 nuclear access is gated to the cell cycle, answering why a constitutive transcription factor only acts at a specific phase.

    Evidence In vitro CDC28-H1 kinase phosphorylation, NLS serine mutagenesis, and localization in S. cerevisiae

    PMID:1652372

    Open questions at the time
    • Did not identify the phosphatase or trigger for late-mitotic dephosphorylation/entry
    • In vitro kinase specificity vs in vivo timing not fully resolved
  2. 1992 High

    Defined Swi5 as a zinc-finger transcriptional activator and showed that target-gene specificity is separable from the DNA-binding module, framing how a shared DNA-recognition fold can drive distinct programs.

    Evidence Gene disruption, promoter-reporter assays, SWI5/ACE2 chimeras, and NMR structures of the zinc fingers in budding yeast

    PMID:1453467 PMID:1453468 PMID:1730413

    Open questions at the time
    • Did not identify the molecular basis of the specificity-conferring region
    • Full-length DNA-bound complex not structurally defined
  3. 1993 High

    Showed cooperative DNA binding with Pho2/Grf10 and that proteolytic instability enforces asymmetric, daughter-cell-restricted HO expression, linking Swi5 abundance control to a developmental outcome.

    Evidence DNA affinity purification, footprinting, cooperative binding assays, and stable-mutant mating-type switching assays

    PMID:7902583 PMID:8355698 PMID:8449406

    Open questions at the time
    • Degradation machinery not identified at this stage
    • Mechanism of cooperativity at atomic level not resolved
  4. 1996 High

    Connected Swi5 nuclear entry to the cell cycle engine by showing it triggers the SIC1 burst that inactivates Clb/Cdk1, and identified EGT2 and Pho85-cyclin targets, establishing Swi5 as the driver of a coordinated M/G1 transcriptional wave.

    Evidence Deletion analysis, mRNA/protein assays, genetic suppression, synchronization, and promoter-reporter assays in S. cerevisiae

    PMID:8668141 PMID:8816483 PMID:9017392 PMID:9529390

    Open questions at the time
    • How concentration thresholds set sharp on/off transcription not mechanistically defined
    • Direct vs indirect target distinctions for some genes incomplete
  5. 1998 Medium

    Mapped a discrete 24-residue Swi5 region required for Pho2 interaction and cooperative binding, demonstrating that HO promoter specificity coincides with the Pho2-interaction surface rather than the zinc fingers.

    Evidence Two-hybrid, in vitro DNA binding, reporter assays, mutagenesis, and chimeric analysis

    PMID:10409653 PMID:9774660

    Open questions at the time
    • Structure of the Swi5-Pho2-DNA cooperative complex not determined
    • Single-lab mapping
  6. 2000 Medium

    Identified Swi5 as a Pho85-cyclin substrate, adding a second kinase input to Swi5 regulation beyond Cdc28.

    Evidence Two-hybrid, in vitro Pho80-Pho85 kinase assay, and genetic lethality in S. cerevisiae

    PMID:10692159

    Open questions at the time
    • Functional consequence of Pho85 phosphorylation sites in vivo not pinpointed
    • Single lab
  7. 2001 High

    Showed Swi5 recruits the Mediator Gal11 module to the HO promoter prior to Pol II, with Swi/Snf required, defining the coactivator-recruitment step of Swi5-driven activation.

    Evidence ChIP of Mediator/Pol II, genetic epistasis, and kinetic binding in budding yeast

    PMID:11562354

    Open questions at the time
    • Direct Swi5-Gal11 contact surface not mapped structurally
    • Generality across other Swi5 targets not established
  8. 2003 High

    Revealed that fission-yeast Swi5 partitions into two functionally distinct complexes — Swi5-Sfr1 (recombination repair) and Swi5-Swi2 (mating-type switching) — separating its roles via shared partner domains.

    Evidence Co-IP, two-hybrid, and genetic epistasis in S. pombe

    PMID:14663140

    Open questions at the time
    • Switch governing complex choice not defined
    • Stoichiometry/structure of complexes not resolved here
  9. 2004 High

    Established the meiotic recombination identity of the small Swi5/Sae3 protein, showing Mei5-Sae3 is required for Dmc1 (not Rad51) chromosome loading and that fission-yeast Swi5 promotes joint-molecule formation.

    Evidence ChIP, immunofluorescence on meiotic chromosomes, sporulation assays, and recombination/epistasis analysis in budding and fission yeast

    PMID:15466419 PMID:15579681 PMID:15620352 PMID:9215889

    Open questions at the time
    • Biochemical mechanism of Dmc1 loading not yet defined
    • Relationship between transcription-factor Swi5 and recombination Swi5 across species reflects orthology rather than one protein
  10. 2006 High

    Demonstrated biochemically that Swi5-Sfr1 stimulates Rhp51/Dmc1 strand exchange substoichiometrically, overcoming RPA inhibition in an ATP-dependent manner, establishing it as a recombination mediator/activator.

    Evidence In vitro strand exchange, ATPase, and ssDNA binding assays with purified S. pombe proteins

    PMID:16921379

    Open questions at the time
    • Molecular step targeted within the filament cycle not yet resolved
    • Single lab
  11. 2009 High

    Showed budding-yeast Mei5-Sae3 binds ssDNA, interacts with RPA, and relieves RPA inhibition to load Dmc1, defining a mediator activity even though Mei5-Sae3 lacks Rad51-mediator and annealing functions.

    Evidence Purified-protein binding, strand assimilation, Co-IP with RPA, and domain mapping

    PMID:19270307 PMID:21543267

    Open questions at the time
    • Why Mei5-Sae3 mediates Dmc1 but not Rad51 not fully explained
    • Single lab
  12. 2007 High

    Placed Swi5-Sfr1 in DNA-damage-induced repair foci dependent on Sfr1 and distinguished it from the Rhp55/57 pathway in crossover outcome, defining its in vivo localization and pathway position.

    Evidence Live GFP microscopy, UV-induced focus formation, and HO-DSB recombination assays in S. pombe

    PMID:17304215

    Open questions at the time
    • Recruitment hierarchy to damage sites only partially defined
    • Single lab
  13. 2010 High

    Demonstrated conservation in mammals: mouse Swi5-Sfr1 forms a mutually stabilizing complex that interacts with Rad51 and is required for homologous recombination and genome stability.

    Evidence Co-IP, in vitro Rad51 pulldown, ES-cell knockouts, survival, SCE, and chromosomal aberration assays

    PMID:20976249

    Open questions at the time
    • In vivo loading sites and kinetics in mammals not defined
    • Physiological role in meiosis vs somatic HR not separated
  14. 2012 High

    Solved the architecture of the complex, showing an elongated crescent-shaped parallel coiled-coil heterodimer that fits the Rad51 filament groove, with Sfr1's N-terminus as the recombinase interface and the rodent RSfp motif as a negative regulator.

    Evidence Crystallography, SAXS, AUC, Fab mapping, and mutagenesis across fission yeast and mouse proteins

    PMID:22033972 PMID:22405003 PMID:22492707

    Open questions at the time
    • Atomic structure of the Swi5-Sfr1-Rad51 filament complex not determined
    • How the disordered Sfr1 N-terminus engages Rad51 not resolved here
  15. 2013 High

    Resolved the mechanistic action on the filament: Swi5-Sfr1 enhances ADP release to sustain the ATP-bound active state, reorients nucleobases via the Rad51 interface, and acts as a dual mediator/activator for Dmc1 opposed by Rad22/Rad52.

    Evidence Optical tweezers, ATPase/ADP-release assays, flow linear dichroism, and competition strand-exchange assays in human and fission yeast systems

    PMID:24078249 PMID:24186976 PMID:24304898

    Open questions at the time
    • Coupling between ADP release and filament stability not fully quantified
    • Single lab for each measurement
  16. 2016 Medium

    Identified a C-terminal SWI5 contribution to RAD51 binding, showed preference for oligomeric RAD51, and proved physical interaction is indispensable for functional stimulation.

    Evidence Co-IP, pulldown, interaction-defective mutagenesis, and strand exchange assays in mouse

    PMID:27131790

    Open questions at the time
    • Relative contributions of Swi5 C-terminus vs Sfr1 N-terminus to the interface not fully partitioned
    • Single lab
  17. 2018 High

    Established at single-molecule resolution that Swi5-Sfr1 reduces recombinase dissociation at both nucleation and maintenance, lowering the nucleation threshold — a mechanism conserved between mouse and fission yeast.

    Evidence Single-molecule TPM and smFRET on Rad51/SpRad51 filaments

    PMID:30297419

    Open questions at the time
    • How dissociation reduction translates to in vivo HR efficiency not quantified
    • Single lab
  18. 2020 High

    Showed the intrinsically disordered Sfr1 N-terminus uses two cooperative Rad51-binding sites and that Swi5-Sfr1 collaborates with Rad55-Rad57 in a higher-order complex, refining the recombinase interface and inter-mediator coordination.

    Evidence NMR, pull-downs, strand exchange, DNA-damage sensitivity, and mutagenesis

    PMID:32204793

    Open questions at the time
    • Structure of the Swi5-Sfr1/Rad55-Rad57 super-complex not determined
    • Single lab
  19. 2023 High

    Established that controlled phosphorylation cycles of the disordered Sfr1 domain tune Swi5-Sfr1 binding to Rad51, with both phosphomimetic and phospho-blocked states impairing repair, defining a regulatory layer over recombinase activation.

    Evidence Phosphomimetic/phospho-null reconstitution, Co-IP, and DNA-damage sensitivity assays; complemented by mechanistic dissection vs Hop2-Mnd1

    PMID:37330173 PMID:37395447

    Open questions at the time
    • The kinase/phosphatase pair controlling Sfr1 phosphorylation cycles not identified
    • In vivo timing of phospho-regulation not mapped
  20. 2024 High

    Refined the mediator mechanism for Dmc1, showing Mei5-Sae3/Swi5-Sfr1 stabilizes early Dmc1 clusters to promote RPA displacement and acts as a nucleation-promoting mediator distinct from the activator mechanism used for Rad51.

    Evidence smFRET, CoSMoS, and real-time kinetic strand-exchange analysis with purified proteins

    PMID:39275989 PMID:39340300

    Open questions at the time
    • Structural basis of the Dmc1/RPA intermediate not resolved
    • Quantitative link to meiotic crossover control incomplete
  21. 2025 Medium

    Extended the stabilization mechanism by showing the complex shifts recombinase oligomeric assembly units (octamer-to-tetramer for RAD51) and stabilizes both ATP- and ADP-bound Dmc1 conformations without inhibiting hydrolysis, defining how it sustains active filaments.

    Evidence Single-molecule TPM step-size analysis (mouse) and Dmc1 conformation/ATPase assays (budding yeast)

    PMID:40682818 PMID:41206037

    Open questions at the time
    • Very recent, single-study findings not yet independently replicated
    • Physiological relevance of oligomeric-state switching not established in vivo

Open questions

Synthesis pass · forward-looking unresolved questions
  • How the two Swi5 identities — a CDK/SCF-regulated zinc-finger transcription factor in budding yeast and the conserved Swi5-Sfr1 recombination mediator in fission yeast/mammals — relate at the level of evolutionary origin and whether any single organism uses both functions remains unresolved in this corpus.
  • No timeline study reconciles the transcription-factor and recombination-mediator orthology groups under one molecular framework
  • Kinase/phosphatase identity for Sfr1 regulation unknown
  • No atomic structure of the recombinase-bound complex

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0098772 molecular function regulator activity 7 GO:0003677 DNA binding 5 GO:0140110 transcription regulator activity 5 GO:0003723 RNA binding 3 GO:0060090 molecular adaptor activity 3
Localization
GO:0005634 nucleus 5 GO:0000228 nuclear chromosome 2
Pathway
R-HSA-73894 DNA Repair 4 R-HSA-1474165 Reproduction 3 R-HSA-1640170 Cell Cycle 3 R-HSA-74160 Gene expression (Transcription) 3
Partners
CDC4DMC1MSN5PHO2PHO85RAD51RPASFR1
Complex memberships
Mei5-Sae3Swi5-Sfr1Swi5-Swi2

Evidence

Reading pass · 41 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1991 CDC28 kinase (Cdk1) directly phosphorylates three serine residues located within or adjacent to the nuclear localization signal (NLS) of S. cerevisiae SWI5, and this phosphorylation is responsible for cell cycle-dependent cytoplasmic retention. Mutation of all three serines results in constitutive nuclear entry; all three are phosphorylated by purified CDC28-dependent H1 kinase activity in vitro. In vitro phosphorylation by purified CDC28-H1 kinase, site-directed mutagenesis of NLS serines, cell fractionation/localization, heterologous NLS fusion Cell High 1652372
1992 SWI5 encodes a zinc finger DNA-binding protein that functions as a transcriptional activator of the HO endonuclease gene. SWI5 and its homolog ACE2 have nearly identical zinc finger regions, bind the same DNA sequences, but activate different gene sets (SWI5→HO; ACE2→CTS1); chimeric fusion experiments show that promoter specificity resides in a domain distinct from the zinc finger domain. Gene disruption/deletion, promoter-reporter assays, chimeric SWI5/ACE2 protein fusions Genes & development High 1730413
1992 NMR structural analysis of two SWI5 zinc-finger domains reveals that finger 2 adopts a classical C2H2 fold, while finger 1 has an additional N-terminal beta strand not seen in other zinc fingers, which stabilizes the folded structure of finger 1. 2D 1H NMR spectroscopy, structure calculation with simulated annealing Journal of molecular biology High 1453468
1992 NMR analysis of SWI5 zinc-finger peptides shows that adjacent zinc-finger domains are structurally independent (flexibly linked); the N-terminal two fingers (fingers 1+2) bind to the 5' end of the DNA binding site, establishing binding polarity. 2D NMR, limited proteolysis, DNA binding assays with one-, two-, and three-finger peptides Journal of molecular biology High 1453467
1993 SWI5 binds the HO promoter cooperatively with the homeodomain protein GRF10 (PHO2/BAS2). The two proteins bind adjacent DNA sites and make unique contacts; the cooperative complex has a longer half-life than either protein alone. GRF10 was purified via cooperative interaction-based DNA affinity chromatography with GST-SWI5. Purification of GST-SWI5 fusion protein; DNA affinity chromatography; methylation interference; missing-nucleoside analysis; in vitro DNA binding/cooperative binding assays Molecular and cellular biology High 7902583 8355698
1993 Rapid proteolytic degradation of SWI5 during early G1 is necessary to prevent HO expression in daughter cells; more stable mutant SWI5 proteins cause daughter cells to switch mating type, demonstrating that SWI5 instability is required for asymmetric HO expression. Stable SWI5 mutant expression, mating-type switching assays, pulse-chase protein stability analysis Genes & development Medium 8449406
1996 Swi5 directly activates transcription of SIC1 (the Cdk inhibitor p40SIC1) at late M phase/early G1 by entering the nucleus at the end of anaphase. Cell cycle-regulated nuclear entry of Swi5 generates the burst of SIC1 transcription required for inactivation of Clb/Cdk1 kinase. SWI5 deletion/mutation analysis, SIC1 mRNA and protein expression assays, genetic suppression (sic1Δ suppresses cdc4 arrest), cell synchronization Molecular and cellular biology High 8816483 9017392
1996 The N-terminal additional beta strand and helix in SWI5 zinc finger 1 (identified by NMR) increase DNA-binding affinity, representing a structural extension that enhances DNA recognition beyond the canonical C2H2 fold. NMR structural analysis, biochemical DNA-binding studies Structure Medium 8736557
1996 Swi5 activates EGT2 transcription immediately upon nuclear entry at the end of mitosis in a concentration-dependent manner; as Swi5 is unstable in the nucleus, its rapid degradation terminates EGT2 transcription before the next cell cycle commitment. Cell cycle synchronization, promoter-reporter assays, SWI5 deletion analysis Molecular and cellular biology Medium 8668141
1997 SAE3 (budding yeast, also called SWI5 in fission yeast context) is a meiosis-specific gene; sae3 mutants produce persistent hyper-resected meiotic DSBs and severely fail to form recombinants, phenotypically similar to dmc1 mutants, indicating SAE3/SWI5 and DMC1 act at the same step of chromosome metabolism. Genetic screen, spore viability, physical monitoring of DSBs and recombinants Genetics Medium 9215889
1998 A 24-amino-acid region of Swi5, upstream of the DNA-binding domain (residues 471–513), is necessary and sufficient for interaction with Pho2 and for cooperative DNA binding at the HO promoter; specific point mutations in this region specifically abolish Pho2-dependent (but not Pho2-independent) gene activation without affecting DNA binding. Two-hybrid assay, in vitro DNA binding, reporter assays, site-directed mutagenesis Molecular and cellular biology Medium 9774660
1998 Swi5 controls transcription of PCL9 and PCL2 in late M phase/telophase; these Pho85-associated cyclins represent the only cyclins expressed at this cell cycle stage. The Swi5 transcription factor thus drives a wave of Pcl-type cyclin synthesis at the end of mitosis. PCL9/PCL2 promoter-reporter assays, SWI5 deletion, Pho85 kinase activity assays, genetic synthetic lethality Molecular biology of the cell Medium 9529390
1999 Chimeric SWI5/ACE2 fusion analysis identifies distinct, separable regions of Swi5 required for HO-specific activation; the Swi5 HO-specificity region coincides with the Pho2-interaction region, demonstrating that promoter specificity is encoded outside the zinc finger DNA-binding domain. Chimeric protein fusions, promoter-reporter assays, in vitro DNA binding The Journal of biological chemistry Medium 10409653
2000 Swi5 interacts physically with Pho85 cyclins (Pcl2 and Pho80) and is phosphorylated in vitro by the Pho80-Pho85 kinase; in pho85 deletion strains, Swi5 activity is misregulated in vivo (overexpression of SWI5 is lethal in pho85Δ), implicating Swi5 as a Pho85 substrate. Two-hybrid screen, in vitro kinase assay with Pho80-Pho85 complex, genetic epistasis/lethality assays Molecular microbiology Medium 10692159
2001 Swi5 recruits the Mediator complex to the HO promoter (1.5 kb upstream of TSS) through specific interaction with the Gal11 module of Mediator, independently of SBF and prior to RNA Pol II binding; Swi/Snf is required for Mediator binding and acts in the same genetic pathway as Mediator for HO activation. Chromatin immunoprecipitation (ChIP) of Mediator and Pol II components, genetic suppression epistasis analysis, kinetic binding experiments Genes & development High 11562354
2003 Fission yeast Swi5 (sp) forms two distinct protein complexes: Swi5-Sfr1 (involved in Rhp51-dependent recombination repair) and Swi5-Swi2 (involved in mating-type switching together with Swi6). Protein interactions with Rhp51 are mediated by a domain common to Swi2 and Sfr1. Genetic epistasis shows these two complexes function in distinct pathways. Co-immunoprecipitation, two-hybrid assays, genetic epistasis analysis Proceedings of the National Academy of Sciences of the United States of America High 14663140
2004 Budding yeast Mei5 (SWI5 ortholog context) and Sae3 form a ternary complex with Dmc1 and are required for Dmc1 (but not Rad51) assembly on chromosomes. Mei5, Sae3, and Dmc1 are mutually dependent for chromosome association; their absence prevents disassembly of Rad51 filaments. Rad51 is required for recruitment of the Mei5-Sae3-Dmc1 complex to chromosomes. Chromatin immunoprecipitation, immunofluorescence on meiotic chromosomes, sporulation/spore viability assays, overexpression suppression Cell High 15579681 15620352
2004 Fission yeast Swi5 (sp) encodes an 85-amino-acid polypeptide with an N-terminal predicted coiled-coil domain. swi5Δ reduces meiotic recombinant frequencies ~10-fold, is hypersensitive to DNA-damaging agents, and acts in a branched pathway of joint molecule formation; swi5Δ suppresses the low spore viability of mus81Δ eme1Δ (joint molecule resolution mutant), placing Swi5 in joint molecule formation. Gene identification/deletion, recombination frequency assays, epistasis analysis with mus81Δ/eme1Δ and rhp55Δ/rhp57Δ Genetics Medium 15466419
2006 The fission yeast Swi5-Sfr1 complex stimulates Rhp51 (Rad51) and Dmc1-mediated DNA strand exchange at substoichiometric concentrations on long DNA substrates; stimulation is completely dependent on RPA and ATP. Swi5-Sfr1 overcomes the inhibitory effect of RPA on recombinase loading and preferentially stimulates the ssDNA-dependent ATPase activity of Rhp51, and increases Dmc1 binding to ssDNA. In vitro strand exchange assay, ATPase assay, ssDNA binding assay with purified proteins Nature structural & molecular biology High 16921379
2007 In fission yeast, Swi5-GFP localizes to the nucleus forming diffuse staining with foci; spontaneous foci require Swi2. Upon UV irradiation, Swi5 foci form in swi2Δ mutants (depending on Sfr1); Sfr1 foci colocalize with damage-induced Rhp51 foci. An HO endonuclease-induced DSB assay showed Rhp51 and Rhp57 (but not Swi5/Sfr1) are essential for crossover production, distinguishing Swi5-Sfr1 from Rhp55/57 in recombination outcome. Live fluorescence microscopy (GFP), UV irradiation-induced focus formation, HO endonuclease DSB assay, genetic analysis The EMBO journal High 17304215
2008 Swi5 is a substrate of the SCF(Cdc4) ubiquitin ligase complex. Swi5 is ubiquitinated and degraded through SCF(Cdc4), and this degradation is required to terminate SIC1 transcription at early G1, ensuring efficient S-phase entry. Stabilized Swi5 causes hyperaccumulation of Sic1 and delays S-phase entry in a manner suppressed by SIC1 deletion. Refined two-hybrid screen under substrate-stabilizing conditions, ubiquitination assay, cell synchronization, S-phase entry assays, SIC1 deletion suppression Proceedings of the National Academy of Sciences of the United States of America Medium 18787112
2009 Budding yeast Mei5-Sae3 complex preferentially binds ssDNA and relieves RPA-imposed inhibition of Dmc1 strand assimilation and DNA binding; Mei5-Sae3 physically interacts with RPA. These results establish Mei5-Sae3 as a mediator (loader) of Dmc1 onto RPA-coated ssDNA. Purified protein in vitro binding assays, strand assimilation assay, Co-IP with RPA The Journal of biological chemistry High 19270307
2010 Mammalian (mouse) Swi5 and Sfr1 are nuclear proteins that form a complex in vivo and in vitro; Swi5 interacts in vitro with Rad51. Both proteins are mutually interdependent for their stability. Loss of either (Swi5−/− or Sfr1−/−) sensitizes ES cells to ionizing radiation, camptothecin, and PARP inhibitor, attenuates SCE induction, and increases chromosome aberrations, demonstrating a role for the mammalian Swi5-Sfr1 complex in homologous recombination. Co-IP, in vitro pulldown with Rad51, ES cell knockout, colony survival assays, SCE assay, chromosomal aberration analysis PLoS genetics High 20976249
2011 The fission yeast Swi5-Sfr1 complex has a 1:1 stoichiometry and displays an extremely elongated dogleg-shaped structure (frictional ratio f/f0 = 2.0) in solution as determined by SAXS and analytical ultracentrifugation; topology mapping with Fab fragments places Sfr1 subdomains at defined positions, suggesting the complex fits into the groove of the Rad51 filament. Analytical ultracentrifugation, ESI-MS, SAXS, Fab-fragment mapping The Journal of biological chemistry High 22033972
2011 The budding yeast Mei5-Sae3 complex preferentially binds a fork-like DNA substrate; Mei5 (not Sae3) confers DNA binding activity; Mei5-Sae3 interacts with Rad51 through the N-terminal domain of Mei5. Mei5-Sae3 lacks recombination mediator activity for Rad51 and lacks ssDNA annealing activity, distinguishing it from Rad52. Purified protein biochemical assays (DNA binding, ssDNA annealing, strand exchange), domain deletion/interaction mapping DNA repair Medium 21543267
2012 Crystal structure of the Swi5-Sfr1 complex reveals that Swi5 and the C-terminal core domain of Sfr1 form a parallel coiled-coil heterodimer joined by two leucine-zipper motifs and a bundle; the coiled coil is sharply kinked creating a crescent-shaped structure for binding within the Rad51 filament groove. The N-terminal region of Sfr1 provides the Rad51-binding interface. X-ray crystallography, functional mutagenesis Structure High 22405003
2012 Mouse Swi5-Sfr1 complex has 1:1 stoichiometry; the intact complex (not Swi5 or Sfr1 alone) physically interacts with Rad51 and stimulates Rad51-mediated homologous DNA pairing by stabilizing the Rad51-ssDNA presynaptic filament. The RSfp (rodent Sfr1 proline-rich) motif in Sfr1 functions as a negative regulatory element. Biophysical stoichiometry determination, Co-IP, in vitro strand exchange assay, presynaptic filament stability assay, mutagenesis of RSfp motif Nucleic acids research High 22492707
2012 Karyopherin Msn5 is required for nuclear export of Swi5 in S. cerevisiae and physically interacts with the N-terminal end of Swi5. Inactivation of Msn5 reduces cellular Swi5 protein levels by a post-transcriptional defect in Swi5 synthesis (not increased degradation). High Swi5 nuclear accumulation in msn5 cells is toxic. GFP localization, Co-IP, mRNA level analysis, protein stability (cycloheximide chase), genetic toxicity assay Biochimica et biophysica acta Medium 22374135
2013 Human SWI5-SFR1 complex enhances ADP release from the RAD51 presynaptic filament (measured by optical tweezers and biochemical assay), thereby stimulating ATP hydrolysis by ssDNA-bound RAD51 and maintaining the catalytically active state of the presynaptic filament. Optical tweezers single-molecule assay, biochemical ATPase/ADP release assay Nucleic acids research High 24078249
2013 Swi5-Sfr1 promotes more perpendicular alignment of nucleobases in the Rad51/ssDNA presynaptic filament (measured by flow linear dichroism); this structural change is mediated through interaction with the Rad51 filament (not directly with DNA), as deletion of the DNA-binding N-terminal Sfr1 domain does not abolish the effect. Flow linear dichroism spectroscopy, deletion mutagenesis of Sfr1 N-terminus Nucleic acids research Medium 24304898
2013 Fission yeast Swi5-Sfr1 acts as both a mediator (loads Dmc1 onto RPA-coated ssDNA) and a direct activator of Dmc1 strand exchange; in contrast, Rad22 (fission yeast Rad52) inhibits Dmc1 activity by competing for binding to RPA-coated ssDNA, demonstrating dual opposing regulation of meiotic recombination. In vitro strand exchange assays, mediator assay, competition assays with purified proteins Genes & development High 24186976
2016 A C-terminal domain within mammalian (mouse) SWI5 contributes to RAD51 interaction; SWI5-SFR1 preferentially associates with the oligomeric form of RAD51. RAD51-interaction-defective mutants of SWI5-SFR1 fail to stimulate Rad51 recombinase activity, establishing that physical interaction is indispensable for functional stimulation. Co-IP, pulldown, mutagenesis, in vitro strand exchange assay Nucleic acids research Medium 27131790
2018 Mouse Swi5-Sfr1 stimulates Rad51 filament assembly by reducing Rad51 dissociation from filaments (both at nucleation and filament maintenance stages), demonstrated at single-molecule level; this reduces the nucleus size from three Rad51 molecules to two. Fission yeast Swi5-Sfr1 similarly specifically reduces SpRad51 disassembly. Single-molecule tethered particle motion (TPM), single-molecule FRET (smFRET) Proceedings of the National Academy of Sciences of the United States of America High 30297419
2020 Two distinct sites within the intrinsically disordered N-terminus of Sfr1 (Sfr1N) cooperatively bind Rad51; deletion of Sfr1N impairs Rad51 stimulation in vitro and causes DNA damage sensitivity. Swi5-Sfr1 and Rad55-Rad57 form a higher-order complex and can collaboratively stimulate Rad51, suggesting they are not fully independent. NMR, in vitro pull-down, strand exchange assay, DNA damage sensitivity assay, mutagenesis eLife High 32204793
2021 Mass spectrometry of Swi5-Sfr1 complex purified from fission yeast meiotic cells identified multiple phosphorylation sites on both Swi5 and Sfr1; phosphomimetic (aspartate) mutants at identified sites are only partially functional, while phospho-null mutants do not impair function, suggesting phosphorylation can negatively modulate but is not required for Swi5-Sfr1 activity. Mass spectrometry of purified meiotic complex, phosphomimetic/phospho-null mutagenesis, functional assays Genes Low 34208949
2023 Phosphorylation of five residues within the intrinsically disordered domain of Sfr1 regulates interaction of Swi5-Sfr1 with Rad51; phosphomimetic Swi5-Sfr1 is defective in both physical and functional interaction with Rad51 and causes DNA repair deficiency. Blocking Sfr1 phosphorylation also causes DNA damage sensitivity, suggesting controlled phosphorylation cycles are important for Rad51-dependent DNA repair. Biochemical reconstitution with phosphomimetic/phospho-null mutants, Co-IP, DNA damage sensitivity assays The Journal of biological chemistry Medium 37330173
2023 Hop2-Mnd1 and Swi5-Sfr1 stimulate Dmc1 filament assembly by distinct mechanisms: Hop2-Mnd1 increases the Dmc1 binding rate (recruits Dmc1 at ssDNA/dsDNA junctions via direct DNA binding), while Swi5-Sfr1 specifically reduces the Dmc1 dissociation rate during nucleation (~2-fold). Together they provide additive stimulation. Single-molecule FRET (smFRET), tethered particle motion (TPM), order-of-addition experiments Nucleic acids research High 37395447
2024 Mei5-Sae3 stabilizes Dmc1 nucleating clusters (2–3 molecules) on naked ssDNA by preferentially reducing Dmc1 dissociation rates; it also stimulates Dmc1 assembly on RPA-coated ssDNA by stabilizing early clusters, which promotes RPA displacement. Coexistence of an intermediate containing both Dmc1 and RPA was directly observed. Single-molecule FRET (smFRET), colocalization single-molecule spectroscopy (CoSMoS), GFP-labeled RPA Nucleic acids research High 39275989
2024 Swi5-Sfr1 stimulates Dmc1-driven strand exchange by acting as a mediator (promotes filament nucleus formation/association with ssDNA) rather than as an activator of the C1-C2 intermediate transition used for Rad51; this mechanistic distinction from Rad51 regulation was established by kinetic real-time analysis identifying three-stranded intermediates. Real-time strand exchange assay with kinetic intermediate analysis, comparison of Dmc1 and Rad51 reactions Nucleic acids research High 39340300
2025 Mouse SWI5-SFR1 reduces the dissociation probability of RAD51 during filament extension and shifts the oligomeric assembly unit from octamers to tetramers, promoting more uniform filament growth; this modulation of RAD51 oligomeric state facilitates extension and stabilizes DNA binding. Single-molecule tethered particle motion (TPM), step-size analysis of RAD51 assembly Nucleic acids research Medium 40682818
2025 Mei5-Sae3 stabilizes Dmc1 filaments in both the active (ATP-bound) and inactive (ADP-bound) allosteric conformations; unlike calcium, AMP-PNP, or the E157D mutation, Mei5-Sae3 stabilizes the active filament without inhibiting ATP hydrolysis (and may enhance ATP hydrolysis). Filament stabilization activity of Mei5-Sae3 does not depend on alteration of the hydrolytic cycle. Dmc1 filament conformation assays, ATPase assays, comparison with known ATP hydrolysis inhibitors, single-molecule approaches Nucleic acids research Medium 41206037

Source papers

Stage 0 corpus · 61 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1991 The role of phosphorylation and the CDC28 protein kinase in cell cycle-regulated nuclear import of the S. cerevisiae transcription factor SWI5. Cell 471 1652372
1992 Parallel pathways of gene regulation: homologous regulators SWI5 and ACE2 differentially control transcription of HO and chitinase. Genes & development 194 1730413
2001 The Swi5 activator recruits the Mediator complex to the HO promoter without RNA polymerase II. Genes & development 116 11562354
2004 A protein complex containing Mei5 and Sae3 promotes the assembly of the meiosis-specific RecA homolog Dmc1. Cell 113 15620352
1996 The transcription factor Swi5 regulates expression of the cyclin kinase inhibitor p40SIC1. Molecular and cellular biology 113 8816483
2003 Two different Swi5-containing protein complexes are involved in mating-type switching and recombination repair in fission yeast. Proceedings of the National Academy of Sciences of the United States of America 106 14663140
2006 The Swi5-Sfr1 complex stimulates Rhp51/Rad51- and Dmc1-mediated DNA strand exchange in vitro. Nature structural & molecular biology 104 16921379
1997 The Swi5 transcription factor of Saccharomyces cerevisiae has a role in exit from mitosis through induction of the cdk-inhibitor Sic1 in telophase. Genetics 93 9017392
1991 ACE2, an activator of yeast metallothionein expression which is homologous to SWI5. Molecular and cellular biology 84 1986241
2004 The budding yeast mei5 and sae3 proteins act together with dmc1 during meiotic recombination. Genetics 77 15579681
1996 EGT2 gene transcription is induced predominantly by Swi5 in early G1. Molecular and cellular biology 76 8668141
2007 Fission yeast Swi5/Sfr1 and Rhp55/Rhp57 differentially regulate Rhp51-dependent recombination outcomes. The EMBO journal 69 17304215
1992 Solution structures of two zinc-finger domains from SWI5 obtained using two-dimensional 1H nuclear magnetic resonance spectroscopy. A zinc-finger structure with a third strand of beta-sheet. Journal of molecular biology 68 1453468
1999 Distinct regions of the Swi5 and Ace2 transcription factors are required for specific gene activation. The Journal of biological chemistry 63 10409653
1993 SWI5 instability may be necessary but is not sufficient for asymmetric HO expression in yeast. Genes & development 57 8449406
1998 Swi5 controls a novel wave of cyclin synthesis in late mitosis. Molecular biology of the cell 51 9529390
1997 Mutations in Saccharomyces cerevisiae that block meiotic prophase chromosome metabolism and confer cell cycle arrest at pachytene identify two new meiosis-specific genes SAE1 and SAE3. Genetics 48 9215889
2009 The Mei5-Sae3 protein complex mediates Dmc1 activity in Saccharomyces cerevisiae. The Journal of biological chemistry 47 19270307
2004 Swi5 acts in meiotic DNA joint molecule formation in Schizosaccharomyces pombe. Genetics 46 15466419
1992 Adjacent zinc-finger motifs in multiple zinc-finger peptides from SWI5 form structurally independent, flexibly linked domains. Journal of molecular biology 46 1453467
2010 Role for the mammalian Swi5-Sfr1 complex in DNA strand break repair through homologous recombination. PLoS genetics 45 20976249
1993 Identification and purification of a protein that binds DNA cooperatively with the yeast SWI5 protein. Molecular and cellular biology 42 8355698
1993 The Swi5 zinc-finger and Grf10 homeodomain proteins bind DNA cooperatively at the yeast HO promoter. Proceedings of the National Academy of Sciences of the United States of America 39 7902583
2012 Mechanistic insights into the activation of Rad51-mediated strand exchange from the structure of a recombination activator, the Swi5-Sfr1 complex. Structure (London, England : 1993) 37 22405003
2012 Rad51 presynaptic filament stabilization function of the mouse Swi5-Sfr1 heterodimeric complex. Nucleic acids research 37 22492707
2006 Different consequences of ACE2 and SWI5 gene disruptions for virulence of pathogenic and nonpathogenic yeasts. Infection and immunity 37 16926418
2002 Mutations in the pho2 (bas2) transcription factor that differentially affect activation with its partner proteins bas1, pho4, and swi5. The Journal of biological chemistry 36 12145299
2008 A refined two-hybrid system reveals that SCF(Cdc4)-dependent degradation of Swi5 contributes to the regulatory mechanism of S-phase entry. Proceedings of the National Academy of Sciences of the United States of America 35 18787112
1996 The solution structure of the first zinc finger domain of SWI5: a novel structural extension to a common fold. Structure (London, England : 1993) 32 8736557
2013 Characterisation of an intrinsically disordered protein complex of Swi5-Sfr1 by ion mobility mass spectrometry and small-angle X-ray scattering. The Analyst 31 23324799
2013 Enhancement of ADP release from the RAD51 presynaptic filament by the SWI5-SFR1 complex. Nucleic acids research 28 24078249
2018 Swi5-Sfr1 stimulates Rad51 recombinase filament assembly by modulating Rad51 dissociation. Proceedings of the National Academy of Sciences of the United States of America 27 30297419
2011 Fission yeast Swi5-Sfr1 protein complex, an activator of Rad51 recombinase, forms an extremely elongated dogleg-shaped structure. The Journal of biological chemistry 25 22033972
2011 The budding yeast Mei5-Sae3 complex interacts with Rad51 and preferentially binds a DNA fork structure. DNA repair 24 21543267
2000 Interactions between Pho85 cyclin-dependent kinase complexes and the Swi5 transcription factor in budding yeast. Molecular microbiology 24 10692159
2017 The differentiated and conserved roles of Swi5-Sfr1 in homologous recombination. FEBS letters 23 28423184
2007 Fission yeast Swi5 protein, a novel DNA recombination mediator. DNA repair 23 17716957
1998 Residues in the Swi5 zinc finger protein that mediate cooperative DNA binding with the Pho2 homeodomain protein. Molecular and cellular biology 23 9774660
2011 An essential role for trimethylguanosine RNA caps in Saccharomyces cerevisiae meiosis and their requirement for splicing of SAE3 and PCH2 meiotic pre-mRNAs. Nucleic acids research 21 21398639
2016 Role of the RAD51-SWI5-SFR1 Ensemble in homologous recombination. Nucleic acids research 16 27131790
1993 Effective long range mapping in Schizosaccharomyces pombe with the help of swi5. Current genetics 16 8221938
2013 Dual regulation of Dmc1-driven DNA strand exchange by Swi5-Sfr1 activation and Rad22 inhibition. Genes & development 15 24186976
2013 Swi5-Sfr1 protein stimulates Rad51-mediated DNA strand exchange reaction through organization of DNA bases in the presynaptic filament. Nucleic acids research 15 24304898
2019 A mutant form of Dmc1 that bypasses the requirement for accessory protein Mei5-Sae3 reveals independent activities of Mei5-Sae3 and Rad51 in Dmc1 filament stability. PLoS genetics 12 31790385
2016 Hop2 and Sae3 Are Required for Dmc1-Mediated Double-Strand Break Repair via Homolog Bias during Meiosis. Molecules and cells 12 27329041
2016 The transcription factor Ace2 and its paralog Swi5 regulate ethanol production during static fermentation through their targets Cts1 and Rps4a in Saccharomyces cerevisiae. FEMS yeast research 11 26975390
2020 Cooperative interactions facilitate stimulation of Rad51 by the Swi5-Sfr1 auxiliary factor complex. eLife 10 32204793
2023 Hop2-Mnd1 and Swi5-Sfr1 stimulate Dmc1 filament assembly using distinct mechanisms. Nucleic acids research 8 37395447
2013 Involvement of Schizosaccharomyces pombe rrp1+ and rrp2+ in the Srs2- and Swi5/Sfr1-dependent pathway in response to DNA damage and replication inhibition. Nucleic acids research 8 23828040
2010 Expression, purification and crystallization of Swi5 and the Swi5-Sfr1 complex from fission yeast. Acta crystallographica. Section F, Structural biology and crystallization communications 7 20823543
2012 Regulation of cell cycle transcription factor Swi5 by karyopherin Msn5. Biochimica et biophysica acta 5 22374135
2021 Mapping and Analysis of Swi5 and Sfr1 Phosphorylation Sites. Genes 4 34208949
2024 Mei5-Sae3 stabilizes Dmc1 nucleating clusters for efficient Dmc1 assembly on RPA-coated single-stranded DNA. Nucleic acids research 3 39275989
2023 Phosphoregulation of DNA repair via the Rad51 auxiliary factor Swi5-Sfr1. The Journal of biological chemistry 3 37330173
2024 Mutational analysis of Mei5, a subunit of Mei5-Sae3 complex, in Dmc1-mediated recombination during yeast meiosis. Genes to cells : devoted to molecular & cellular mechanisms 2 38924305
2023 The role of conserved amino acid residues of Sae3 in Mei5-Sae3 complex for Dmc1 assembly in meiotic recombination. Genes & genetic systems 2 37225456
2019 Karyopherin Msn5 is involved in a novel mechanism controlling the cellular level of cell cycle regulators Cln2 and Swi5. Cell cycle (Georgetown, Tex.) 2 30739521
2016 Downregulation of SWI5 and CTC1 genes: hepatitis B virus DNA polymerase transactivated protein 1-mediated inhibition of DNA repair. Acta virologica 2 27265469
2024 The Swi5-Sfr1 complex regulates Dmc1- and Rad51-driven DNA strand exchange proceeding through two distinct three-stranded intermediates by different mechanisms. Nucleic acids research 1 39340300
2025 SWI5-SFR1 reduces RAD51 recombinase extending units during filament assembly. Nucleic acids research 0 40682818
2025 Mei5-Sae3 stabilizes both active and inactive forms of Dmc1 filaments independently of its impact on ATP hydrolysis. Nucleic acids research 0 41206037

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