Affinage

RAD51

DNA repair protein RAD51 homolog 1 · UniProt Q06609

Length
339 aa
Mass
37.0 kDa
Annotated
2026-06-10
100 papers in source corpus 45 papers cited in narrative 45 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 8/8 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

RAD51 is the central eukaryotic recombinase that assembles as an ATP-dependent nucleoprotein filament on single-stranded DNA and catalyzes homology search and DNA strand exchange, the core reaction of homologous recombination (PMID:9012806). Filament assembly on RPA-coated ssDNA is rate-limited by nucleation, which BRCA2 overcomes by chaperoning a preassembled RAD51 nucleus onto ssDNA, displacing RPA and stabilizing the filament against ATP hydrolysis (PMID:20729832, PMID:36976771); a C-terminal BRCA2 TR2 motif braces adjacent protomers across the filament interface, while the BRC repeats engage distinct RAD51 surfaces (PMID:37919288, PMID:15937124). The filament's recombinase activity is intrinsically coupled to ATP hydrolysis and to an inter-subunit ATP cap that tunes turnover versus strand-exchange efficiency (PMID:9012806, PMID:22275364), and Loop2 residues impose strict mismatch intolerance that distinguishes RAD51 from its meiotic counterpart DMC1 (PMID:34871438). A broad network of mediators governs the filament: RAD52 targets RAD51 to RPA-ssDNA and channels lesions between strand invasion and annealing (PMID:9450760, PMID:9450758, PMID:18337252), Rad54 stimulates homologous pairing and branch migration and drives ATPase-dependent filament turnover from duplex DNA (PMID:9590697, PMID:17567608, PMID:18617519), the RAD51 paralogs assemble into complexes that remodel and stabilize presynaptic filaments (PMID:10749867, PMID:26186187, PMID:23810717), and HOP2-MND1 and FANCD2/FANCI further stimulate or stabilize the filament (PMID:24943459, PMID:27694619, PMID:37526271). Filament abundance at replication forks is set antagonistically by RADX, which competes for ssDNA, stimulates RAD51 ATPase, and destabilizes filaments in opposition to BRCA2 (PMID:30021152, PMID:33453169, PMID:32621611). Chromatin loading is controlled by post-translational modification, including TOPBP1/PLK1-dependent Ser14 phosphorylation, Mec1-dependent phosphorylation of the yeast enzyme, and TOPORS-dependent SUMOylation (PMID:26811421, PMID:21738226, PMID:35061896). Beyond canonical double-strand break repair and break-induced replication (PMID:14993274), RAD51 protects stalled and nascent replication forks—catalyzing fork reversal while bypassing the bound CMG helicase, shielding abasic sites and nascent strands from MRE11/DNA2/EXO1 nucleases, and suppressing transcription-replication conflicts (PMID:37104614, PMID:39178838, PMID:37526271, PMID:36002000); in its absence, MRE11-driven degradation of unprotected nascent DNA releases cytosolic fragments that activate STING-mediated innate immunity (PMID:28334891). RAD51 also promotes mitotic DNA synthesis and centromere integrity (PMID:34508092, PMID:36702125) and forms TERRA R-loops at telomeres (PMID:33057192).

Mechanistic history

Synthesis pass · year-by-year structured walk · 14 steps
  1. 1997 High

    Establishing that purified human RAD51 is itself a recombinase defined the protein's core catalytic activity and its mechanistic relationship to bacterial RecA.

    Evidence In vitro ATPase, homologous pairing, and strand exchange assays with purified HsRad51 under ATP and ATP-γS

    PMID:9012806

    Open questions at the time
    • Did not address how the slow human enzyme is regulated in cells
    • No structure of the active filament
    • Mediators required for activity on RPA-coated ssDNA not identified
  2. 1998 High

    Identifying Rad52 and Rad54 as direct RAD51 stimulators showed the recombinase does not act alone but requires mediators to load onto RPA-ssDNA and to complete pairing.

    Evidence In vitro strand exchange, homologous pairing, and ATPase assays with purified yeast and human Rad51, Rad52, Rad54, and RPA

    PMID:9012806 PMID:9450758 PMID:9450760 PMID:9590697

    Open questions at the time
    • Did not define the in vivo order of mediator action
    • Structural basis of Rad51-Rad52 and Rad51-Rad54 contacts unresolved
    • Did not explain how channeling between invasion and annealing is decided
  3. 1999 Medium

    Mapping the RAD51 C-terminal residues required for RAD52 binding linked a specific protein-protein interaction to cooperative homologous pairing.

    Evidence Yeast two-hybrid, random mutagenesis, and in vitro pairing assays with the F259V mutant

    PMID:10448035

    Open questions at the time
    • Single interface mapped without structure
    • Did not test consequences in cells
    • Other RAD52 contacts not excluded
  4. 2000 Medium

    Live-cell relocalization to damaged postreplicative chromatin connected RAD51 biochemistry to a cellular site of action in S-phase repair.

    Evidence UV microirradiation with halogenated thymidine labeling and immunofluorescence

    PMID:10908572

    Open questions at the time
    • Correlative localization, not direct demonstration of repair
    • Recruitment factors not identified
    • Single lab
  5. 2004 Medium

    Genetic requirement for RAD51 in break-induced replication extended its role beyond gene conversion to replication-associated repair.

    Evidence Chromosome fragmentation assay and rad51 epistasis in S. cerevisiae

    PMID:14993274

    Open questions at the time
    • Yeast genetics, not direct biochemical mechanism
    • Did not define the replication machinery coupling
    • Human relevance not tested here
  6. 2008 High

    Defining how RAD51 inhibits RAD52 annealing and stimulates Rad54 branch migration showed the filament actively partitions DSBs between recombination subpathways.

    Evidence In vitro annealing and branch migration assays with purified Rad51, Rad52, Rad59, Rad54, and conformation comparisons

    PMID:18337252 PMID:18617519

    Open questions at the time
    • In vitro only
    • In vivo pathway-choice control not established
    • Role of additional regulators in channeling not addressed
  7. 2015 High

    Demonstrating that the RAD51 paralog complex remodels presynaptic filaments to a stabilized open conformation defined a mechanistic role for paralogs distinct from BRCA2-mediated nucleation.

    Evidence Filament remodeling, single-molecule imaging, EM, and Walker-box mutagenesis of C. elegans RFS-1/RIP-1

    PMID:10749867 PMID:23810717 PMID:26186187

    Open questions at the time
    • Human paralog complex stoichiometry not fully resolved
    • Structural basis of remodeling unknown
    • Coordination with BRCA2 in vivo not defined
  8. 2016 Medium

    Identifying TOPBP1/PLK1-dependent Ser14 phosphorylation and TOPORS-dependent SUMOylation established post-translational control of RAD51 chromatin loading.

    Evidence siRNA screens, phosphorylation/SUMO site mapping, chromatin fractionation, and foci assays

    PMID:21738226 PMID:26811421 PMID:35061896

    Open questions at the time
    • How modifications mechanistically alter filament assembly not fully resolved
    • Crosstalk between phosphorylation and SUMOylation untested
    • Modification dynamics during repair not measured
  9. 2017 Medium

    Linking RAD51 loss to MRE11-driven nascent-DNA degradation and cytosolic self-DNA accumulation connected fork protection to STING innate immune signaling.

    Evidence RAD51 knockdown, cytosolic DNA detection, STING activation, and MRE11 epistasis

    PMID:28334891

    Open questions at the time
    • Knockdown rather than separation-of-function alleles
    • Quantitative link between fork protection defect and immune output not established
    • In vivo relevance not tested
  10. 2018 Medium

    Establishing RADX as a ssDNA-competing antagonist that opposes BRCA2 defined how filament abundance at forks is tuned downward.

    Evidence siRNA, RADX overexpression, DNA fiber assays, and epistasis across multiple HR-deficient backgrounds

    PMID:30021152 PMID:32621611

    Open questions at the time
    • Cellular epistasis preceded full biochemical mechanism
    • Conditions favoring RADX over BRCA2 unclear
    • Regulation of RADX itself not addressed
  11. 2021 High

    Reconstituting RADX with purified RAD51 showed it selectively binds ATP-bound RAD51, stimulates ATP hydrolysis, and destabilizes filaments, placing it in direct functional opposition to BRCA2.

    Evidence In vitro strand exchange, D-loop, ATPase, and single-molecule assays with purified proteins

    PMID:33453169

    Open questions at the time
    • Structural basis of RADX-RAD51 selectivity unknown
    • Switch between RADX and BRCA2 dominance in vivo not defined
    • Fork-specific recruitment not resolved
  12. 2021 Medium

    Expanding RAD51's roles to mitotic DNA synthesis, transcription-replication conflict suppression, telomeric TERRA R-loop formation, and HELQ stimulation broadened the recombinase into a general genome-protection factor.

    Evidence Acute RAD51/PLK1 inhibition, MiDAS and fiber assays, in vitro R-loop and helicase reconstitution, single-molecule imaging

    PMID:33057192 PMID:34508092 PMID:34937945 PMID:36002000

    Open questions at the time
    • Whether these functions use the canonical filament or distinct assemblies is partly unresolved
    • In vivo contributions of each function not quantitatively partitioned
    • Mostly single-lab demonstrations
  13. 2023 High

    Mechanistic resolution of fork reversal and in-cell filament dynamics showed RAD51 strand exchange generates a parental duplex behind the bound CMG helicase and that filaments scan the nucleus via compaction-extension cycles.

    Evidence CMG degron and fiber assays in human cells; in vivo single-molecule tracking of endogenously tagged Rad51 in yeast with rad54/srs2 mutants

    PMID:37104614 PMID:37605042

    Open questions at the time
    • Structure of the RAD51-CMG-fork intermediate unknown
    • How filament shape is read out for homology search not resolved
    • Human in vivo filament dynamics not directly imaged
  14. 2024 High

    Structural and functional demonstration that RAD51 recognizes and protects abasic sites refined its fork-protection role to specific lesion types.

    Evidence Cryo-EM of RAD51 on abasic DNA, Xenopus extract and human cell experiments, fiber and nuclease protection assays

    PMID:37526271 PMID:39178838

    Open questions at the time
    • How abasic recognition is regulated by mediators unclear
    • Relationship to ATPase cycle not fully defined
    • In vivo abundance of abasic-protected filaments unknown

Open questions

Synthesis pass · forward-looking unresolved questions
  • It remains unresolved how the competing mediator and antagonist network, post-translational modifications, and lesion-specific recognition are integrated to determine RAD51 filament fate at any given genomic site.
  • No unified structural model of the regulated filament in its cellular context
  • Quantitative thresholds for BRCA2-versus-RADX dominance unknown
  • How modification state biases between repair, fork protection, and immune signaling not established

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0003677 DNA binding 4 GO:0140097 catalytic activity, acting on DNA 3 GO:0140657 ATP-dependent activity 3 GO:0003723 RNA binding 1
Localization
GO:0000228 nuclear chromosome 4 GO:0005634 nucleus 2
Pathway
R-HSA-69306 DNA Replication 3 R-HSA-73894 DNA Repair 3 R-HSA-1640170 Cell Cycle 2 R-HSA-168256 Immune System 1
Partners
BRCA2DMC1FANCD2HELQRAD51CRAD52RAD54RADX
Complex memberships
RAD51 paralog complex (RAD51B-RAD51C)RAD51-ssDNA presynaptic nucleoprotein filament

Evidence

Reading pass · 45 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2010 Purified full-length human BRCA2 promotes assembly of RAD51 onto single-stranded DNA (ssDNA) by targeting RAD51 to ssDNA over double-stranded DNA, enabling RAD51 to displace RPA from ssDNA, and stabilizing RAD51-ssDNA filaments by blocking ATP hydrolysis. BRCA2 does not mediate ssDNA annealing. Biochemical reconstitution with purified full-length BRCA2 and RAD51; strand-exchange assays, RPA displacement assays, ATP hydrolysis measurements Nature High 20729832
1998 Yeast Rad52 protein stimulates DNA strand exchange by Rad51 by targeting Rad51 to RPA-coated ssDNA, overcoming the inhibitory effect of RPA on presynaptic filament formation; stimulation requires concerted action of Rad51, Rad52, and RPA via specific protein-protein interactions. In vitro DNA strand exchange assays with purified yeast Rad51, Rad52, and RPA; protein interaction studies Nature High 9450758 9450760
1998 Yeast Rad54 protein physically interacts with Rad51 and strongly stimulates the rate of homologous DNA pairing between ssDNA and dsDNA catalyzed by Rad51; Rad54 possesses a dsDNA-dependent ATPase activity. Purification of Rad54 to near homogeneity; in vitro homologous pairing assays; ATPase assays; protein interaction studies Nature High 9590697
1997 Purified human RAD51 (HsRad51) catalyzes ATP-dependent homologous pairing and DNA strand exchange in vitro; rates of ATP hydrolysis, homologous pairing, and strand exchange by HsRad51 are less than 1/10 those of RecA. In the presence of ATP-γS, HsRad51 forms stable presynaptic complexes and promotes renaturation but does not catalyze strand exchange or homologous pairing with duplex DNA, suggesting that homologous pairing and strand exchange by HsRad51 are more closely linked to ATP hydrolysis than in RecA. In vitro biochemical assays with purified HsRad51; ATPase assays, homologous pairing, strand exchange assays with ATP and ATP-γS Proceedings of the National Academy of Sciences of the United States of America High 9012806
1998 Human Rad52 stimulates homologous pairing by human Rad51; hRad52 binds ssDNA and is involved in an early stage of Rad51-mediated recombination. In vitro homologous pairing assays with purified hRad51 and hRad52 Nature High 9450758
2005 BRCA2 BRC repeats (BRC3 and BRC4) bind RAD51-DNA nucleoprotein filaments at lower molar ratios and only disrupt filaments at high concentrations. BRC3 contacts the N-terminal domain of RAD51 and BRC4 contacts the nucleotide-binding core, showing that BRC repeats are non-equivalent in their mode of interaction with RAD51 filaments. Cryo-EM structural analysis of RAD51-DNA filaments with BRC peptides; biochemical binding assays Proceedings of the National Academy of Sciences of the United States of America High 15937124
2000 Human Rad51 redistributes to selectively UV-damaged, halogenated-thymidine-labeled chromatin after UV microirradiation, with recruitment occurring from pre-existing S-phase nuclear foci. Rad51 foci associate preferentially with postreplicative rather than replicating chromatin, supporting a role in recombinational repair of damage in postreplicative chromatin. UV microirradiation of small nuclear areas combined with halogenated thymidine labeling and immunofluorescence; confocal microscopy The Journal of cell biology Medium 10908572
2004 RAD51 is required for more than 95% of break-induced replication (BIR) events at unique chromosomal sequences in yeast, demonstrating a genetic requirement for RAD51 in strand invasion during BIR. Chromosome fragmentation assay in S. cerevisiae; genetic epistasis analysis using rad51 deletion mutants Molecular and cellular biology Medium 14993274
2000 Human RAD51 paralogs (XRCC2, XRCC3, RAD51B, RAD51C, RAD51D) form simultaneous protein interactions with each other and with HsRAD51; three-hybrid and baculovirus co-purification experiments show that some interactions (e.g., RAD51B-RAD51D) require a third paralog (RAD51C) to occur, suggesting they may form multi-protein complexes. Yeast two-hybrid, yeast three-hybrid, and baculovirus co-purification with 6xHis-tagged proteins The Journal of biological chemistry Medium 10749867
1999 The C-terminal region of HsRad51 contains amino acid residues required for binding to HsRad52; mutations in this region (not the N-terminal domain) impair HsRad52 binding. The HsRad51 F259V mutation, which abrogates HsRad52 binding, reduces the stimulation of homologous pairing that occurs with both proteins together without affecting HsRad51-only pairing, establishing that the HsRad51-HsRad52 interaction is important for cooperative homologous pairing. Yeast two-hybrid analysis; random mutagenesis; in vitro homologous pairing assays with purified mutant and wild-type proteins Journal of molecular biology Medium 10448035
2007 Efficient turnover of Rad51 from dsDNA after strand exchange requires both the Rad51 ATPase activity and the Rad54 ATPase activity; the catalytic efficiency of Rad54's ATPase is stimulated by Rad51 partial filaments on dsDNA. The Rad51-K191R ATPase-dead mutant forms filaments with significantly increased stability on DNA. Kinetic ATPase assays; electron microscopy of nucleoprotein filaments; experiments with wild-type Rad51, Rad51-K191R mutant, and Rad54 proteins Nucleic acids research Medium 17567608
2008 Rad51 inhibits Rad52-mediated annealing of complementary ssDNA in an ATP-dependent manner through specific protein-protein interaction; the Rad51 nucleoprotein filament is more inhibitory than free Rad51. Rad59 partially restores Rad52 annealing in the presence of Rad51, suggesting coordinated channeling of processed DSBs to either strand invasion or annealing pathways. In vitro ssDNA annealing assays with purified yeast Rad51, Rad52, Rad59, and RPA; protein interaction studies The Journal of biological chemistry High 18337252
2008 Human Rad51 specifically stimulates the branch migration activity of human Rad54 through protein-protein interactions; the active conformation of the hRad51 filament is more stimulatory than the inactive form. This stimulation is evolutionarily conserved (also observed with yeast proteins). In vitro branch migration assays with purified hRad51, hRad54, yeast Rad51, and Rad54; protein interaction assays The Journal of biological chemistry Medium 18617519
2009 Human PSF directly interacts with RAD51 through its N-terminal region and modulates RAD51-mediated homologous pairing and strand exchange in a concentration-dependent biphasic manner: stimulating at low RAD51 concentrations and inhibiting at optimal RAD51 concentrations. Co-immunoprecipitation; in vitro homologous pairing and strand exchange assays with purified PSF and RAD51; deletion analysis Nucleic acids research Medium 19447914
2015 The C. elegans RAD51 paralog complex RFS-1/RIP-1 binds pre-synaptic RAD51 filaments and remodels them to a stabilized, 'open,' and flexible conformation in which ssDNA is more accessible and RAD51 dissociation rate is reduced. Walker box mutations in RFS-1 that abolish filament remodeling also abolish stimulation of RAD51 strand exchange, demonstrating that remodeling activity is essential for function. Biochemical filament remodeling assays; single-molecule imaging; electron microscopy; mutagenesis of Walker box motifs Cell High 26186187
2016 TOPBP1 promotes PLK1 kinase-mediated phosphorylation of RAD51 at serine 14, which is required for RAD51 recruitment to chromatin (chromatin loading and foci formation) during homologous recombination repair; TOPBP1 BRCT domains 7/8 are essential for RAD51 foci formation. siRNA screen; co-immunoprecipitation; chromatin fractionation; RAD51 foci assays; phosphorylation mapping The Journal of cell biology Medium 26811421
2018 RADX antagonizes RAD51 by competing with RAD51 for binding to ssDNA, modulating the amount of RAD51 at stalled replication forks. Loss of RADX restores fork protection in BRCA1-, BRCA2-, FANCA-, FANCD2-, or BOD1L-deficient cells; overexpression of RADX causes fork degradation dependent on MRE11 and DNA2 nucleases and fork reversal. siRNA knockdown, RADX overexpression, DNA fiber assays, epistasis analysis in multiple HR-deficient backgrounds Cell reports Medium 30021152
2021 RADX directly and selectively interacts with ATP-bound RAD51, stimulates RAD51 ATP hydrolysis, and destabilizes RAD51 nucleofilaments, thereby inhibiting RAD51 strand exchange and D-loop formation. BRCA2 can overcome RADX-dependent RAD51 inhibition, placing RADX in functional opposition to BRCA2 in regulating RAD51 nucleofilament stability during DNA replication. In vitro strand exchange and D-loop assays with purified proteins; direct binding assays with ATP-bound RAD51; ATPase stimulation assays; single-molecule imaging; DNA fiber assays Molecular cell High 33453169
2020 RADX condenses ssDNA filaments (including RPA-coated ssDNA) via higher-order assemblies, blocks RPA displacement by RAD51, and prevents RAD51 loading onto ssDNA, functioning as a negative regulator of RAD51 filament formation. Single-molecule imaging of purified proteins on ssDNA curtains; in vitro RAD51 loading assays Nucleic acids research High 32621611
2023 RAD51 uses its strand exchange activity to bypass the CMG replicative helicase (which remains bound to a stalled fork) during replication fork reversal. If the helicase is unloaded, RAD51 is no longer required for fork reversal. Thus RAD51 creates a parental DNA duplex behind the helicase that DNA translocases use for branch migration to generate the reversed fork structure. Auxin-inducible degron (AID) system to deplete CMG components; DNA fiber assays; epistasis analysis in human cells Science (New York, N.Y.) Medium 37104614
2017 RAD51 deficiency leads to accumulation of self-DNA in the cytoplasm, triggering a STING-mediated innate immune response; the unprotected nascent genome in RAD51-deficient cells is degraded by MRE11 exonuclease, and the resulting fragmented nascent DNA accumulates in the cytosol to initiate innate immune signaling. RAD51 siRNA knockdown; cytosolic DNA detection; STING pathway activation assays; epistasis with MRE11 inhibition Nucleic acids research Medium 28334891
2016 FANCI-FANCD2 (I-D) complex directly binds RAD51 and stabilizes the RAD51-DNA filament in a manner requiring the DNA-binding activity of FANCI; the stabilized filament protects the 5'-DNA end from FAN1 nucleolytic degradation. The RAD51 mutant from FANCR patient cells fails to achieve this protection. Co-immunoprecipitation; in vitro RAD51 filament stability assays with purified I-D complex; nuclease protection assays; patient-derived RAD51 mutant analysis Nucleic acids research Medium 27694619
2014 HOP2-MND1 heterodimer stimulates RAD51 DNA strand exchange by inducing conformational changes in RAD51 that enhance interaction with nucleotide cofactors, modify DNA-binding specificity, facilitate RAD51 loading onto ssDNA, and promote dsDNA binding during the homology search; HOP2-MND1 enables strand exchange in the absence of divalent metal ions and offsets the K133A ATP-binding mutation. In vitro strand exchange assays; nucleotide binding assays; DNA binding specificity assays with purified RAD51 and HOP2-MND1 Nature communications High 24943459
2012 The conserved aspartate at the inter-subunit ATP cap (Asp-316 in human RAD51) forms a salt bridge with the ATP γ-phosphate in the nucleoprotein filament, enhancing filament turnover at the expense of recombinase activity; substitution of Asp-316 with lysine (HsRAD51-D316K) decreases NPF turnover and markedly improves strand exchange activity in the absence of salt. Biochemical nucleoprotein filament assays; strand exchange assays; electron microscopy of archaebacterial RadA and human RAD51 D316K mutant filaments The Journal of biological chemistry High 22275364
2011 Yeast Rad51 is phosphorylated on Ser192 in a DNA-damage-responsive manner primarily mediated by the Mec1 kinase; Ser192 Ala and Glu mutations confer hypersensitivity to DNA damage and homologous recombination defects. Ser192 is required for Rad51 ATPase activity and DNA-binding activity in vitro but not for multimer formation. In vivo phosphorylation mapping; in vitro ATPase and DNA-binding assays with Ser192 mutants; DNA damage sensitivity assays EMBO reports Medium 21738226
2013 The HsRAD51B-HsRAD51C heterodimer forms a stable complex on ssDNA and partially stabilizes HsRAD51 nucleoprotein filaments against BLM helicase anti-recombinogenic activity; HsRAD51B-HsRAD51C also stimulates HsRAD51-mediated D-loop formation in the presence of RPA but does not facilitate RAD51 nucleation on RPA-coated ssDNA. In vitro filament stability assays; D-loop assays with purified HsRAD51, HsRAD51B-HsRAD51C, RPA, and BLM DNA repair Medium 23810717
2022 TOPORS acts as a SUMO E3 ligase that SUMOylates RAD51 at lysine residues 57 and 70 in response to DNA damage; TOPORS SUMOylation is facilitated by ATM-induced phosphorylation of TOPORS at Thr515. SUMOylation of RAD51 is required for its chromatin recruitment and homologous recombination repair; SUMOylation-deficient RAD51 has reduced association with BRCA2. Mass spectrometry identification of SUMOylation sites; TOPORS knockdown; mutant (K57R/K70R) RAD51 expression; chromatin fractionation; RAD51 foci assays; Co-IP of RAD51 with BRCA2 Nucleic acids research Medium 35061896
2021 RAD51 protects under-replicated DNA in mitotic cells and promotes mitotic DNA synthesis (MiDAS) and successful chromosome segregation; MiDAS requires de novo RAD51 recruitment to ssDNA supported by Polo-like kinase 1 (PLK1)-mediated phosphorylation of RAD51. Acute inhibition of MiDAS delays anaphase onset and induces centromere fragility. Acute RAD51 inhibition; EdU incorporation assays for MiDAS; PLK1 inhibition; live-cell imaging; centromere fragility quantification Nature communications Medium 34508092
2023 BRCA2's C-terminal TR2 motif binds across the protomer interface in the RAD51 nucleoprotein filament, acting as a brace for adjacent RAD51 molecules by targeting an acidic-patch motif on RAD51; structure-guided mutagenesis validated the functional importance of this interaction for filament stabilization. Cryo-electron microscopy of RAD51-TR2 complexes; structure-guided mutagenesis Nature communications High 37919288
2023 BRCA2 accelerates nucleation of RAD51 onto RPA-coated ssDNA to a rate approaching RAD51 association with naked ssDNA, eliminating the rate-limiting nucleation step by chaperoning a short preassembled RAD51 filament onto the ssDNA; a RAD51 dimer is the minimal unit required for spontaneous nucleation but growth self-terminates below the diffraction limit in the absence of BRCA2. Single-molecule microfluidics, microscopy, and micromanipulation with full-length BRCA2 and RAD51 on individual DNA molecules mimicking resected lesions Proceedings of the National Academy of Sciences of the United States of America High 36976771
2024 RAD51 nucleofilaments specifically recognize and protect abasic sites in ssDNA; abasic sites increase the RAD51 association rate to DNA. In the absence of BRCA2 or RAD51, abasic sites accumulate and induce abasic ssDNA gaps that make replicating DNA fibers sensitive to APE1. RAD51 assembled on abasic DNA prevents cleavage by the MRE11-RAD50 complex, suppressing replication fork breakage. Cryo-EM structure of RAD51 on abasic-site-containing DNA; Xenopus egg extract experiments; human cell experiments; DNA fiber assays; nuclease protection assays Molecular cell High 39178838
2021 RAD51 physically interacts with TERRA lncRNA and catalyzes R-loop formation with TERRA in vitro, directly promoting TERRA recruitment to telomeres by strand invasion in trans; this process is counteracted by RNaseH1 and TRF1. In vitro R-loop formation assay with purified RAD51 and TERRA; reporter system for TERRA-telomere association; RNaseH1/TRF1 counteraction assays Nature Medium 33057192
2021 RAD51 helicase HELQ is strongly stimulated by RAD51 during DNA unwinding via direct complex formation; conversely, RPA inhibits HELQ DNA unwinding but stimulates its DNA strand annealing activity. Biochemical helicase and annealing assays with purified HELQ, RAD51, and RPA; single-molecule imaging; Co-IP Nature Medium 34937945
2021 FANCD2, independent of FANCI dimerization, stabilizes RAD51 filaments to inhibit DNA2, MRE11, and EXO1 nucleases at stalled replication forks; additionally, FANCD2 acts as a RAD51 mediator to stimulate RAD51 strand exchange activity, providing a mechanistic link between FANCD2 and BRCA2 in the FA/BRCA fork protection pathway. In vitro nuclease protection assays and strand exchange assays with purified FANCD2, RAD51, DNA2, MRE11, EXO1; RAD51 filament stability assays Nucleic acids research Medium 37526271
1998 HsRad51 is proteolytically cleaved during apoptosis in human T-lymphocyte cell lines with similar kinetics to PARP cleavage; cleavage is blocked by the caspase inhibitor Ac-DEVD-CHO, implicating a DEVD-specific caspase, though purified caspases 2, 3, or 6-10 could not individually cleave HsRad51 in vitro. Immunoblotting of apoptotic cell lysates; cell-free apoptosis system with IVT-HsRad51; caspase inhibitor experiments FEBS letters Medium 9607320
2001 Depletion of HsRad51 from human cell-free extracts diminishes triplex-induced recombination, and supplementation with purified HsRad51 restores it, establishing that HsRad51 is required for triplex-induced intermolecular recombination in human cell extracts. Immunodepletion and reconstitution in human cell-free extracts; supF reporter assay for recombination The Journal of biological chemistry Medium 11278954
2022 RAD51 Cys319 is a functionally significant redox-regulated site; oxidation of Cys319 disrupts DNA binding (molecular dynamics simulations show DNA dissociation from oxidized Cys319 RAD51 filament). Peroxiredoxin 1 (PRDX1) maintains Cys319 in a reduced state, and loss of PRDX1 leads to increased sulfenylation of RAD51 Cys319, impaired RAD51 foci formation, and decreased homologous recombination. Cys319 mutagenesis; molecular dynamics simulation; sulfenylation probe (DAz-2) labeling in PRDX1-deficient cells; RAD51 foci assays; HR reporter assays Redox biology Medium 36058112
2023 Centromeric DNA breaks in quiescent human cells are resolved enzymatically by RAD51 recombinase, which safeguards the specification of functional centromeres. Single-cell imaging strategy for DNA breaks at repetitive centromeric regions; RAD51 inhibition in quiescent cells; centromere integrity assays Molecular cell Medium 36702125
2021 RAD51 protects replication forks from transcription-replication conflicts (TRCs); RAD51-deficient regions enriched for early-S-phase replication and transcription show increased fork breakage, and inhibiting early S-phase transcription ameliorates many adverse effects of RAD51 depletion. RAD51 depletion; DNA fiber assays; transcription inhibition epistasis; genomic mapping of affected loci Molecular cell Medium 36002000
2021 Cryo-EM structures of human RAD51-DNA complexes reveal that Loop2 residues V273 and D274 in RAD51 (vs. P274 and G275 in DMC1) are key determinants of mismatch intolerance during strand exchange; these differences in Loop2 that contact both ssDNA and the complementary strand explain why RAD51 does not permit HR in the presence of mismatches whereas DMC1 does. Cryo-EM structures of Rad51-DNA and Dmc1-DNA complexes; molecular dynamics simulation; single-molecule FRET assays; site-directed mutagenesis Nucleic acids research High 34871438
2023 In vivo, Rad51-ssDNA nucleoprotein filaments in budding yeast span the entire nucleus following DSB induction, adopting diverse shapes not seen in vitro; the filaments undergo cycles of compaction and extension modulated by Rad54 (promotes extension) and Srs2 (promotes compaction), and this compaction-extension dynamic constitutes a robust nuclear homology search strategy. Functional fluorescently tagged Rad51 expressed from endogenous locus; live-cell single-molecule imaging; DSB induction; genetic analysis with rad54 and srs2 mutants; biophysical modeling Nature structural & molecular biology High 37605042
2020 Rad51 facilitates Dmc1 nucleoprotein filament assembly during meiosis through direct physical interaction; Dmc1 nucleation is stimulated by short Rad51 patches on DNA, and pull-down assays confirm a physical interaction between ScDmc1 and ScRad51 but not between ScDmc1 and EcRecA. Single-molecule tethered particle motion assays for filament assembly kinetics; in vitro biochemical filament assays; pull-down experiments with purified proteins Proceedings of the National Academy of Sciences of the United States of America Medium 32404423
2018 Rad51 and Dmc1 have an intrinsic ability to self-segregate within mixed presynaptic filaments in vitro, without any accessory proteins; Dmc1 stabilizes adjacent Rad51 filament segments, suggesting cross-talk between the two recombinases. Single-molecule imaging of Rad51 and Dmc1 presynaptic complex assembly on ssDNA curtains The Journal of biological chemistry Medium 29382724
2017 Human RAD52 binds tightly to RPA-ssDNA and imposes an inhibitory effect on RPA turnover; during RAD51 presynaptic complex assembly, most RPA and RAD52 are displaced but some RAD52-RPA-ssDNA clusters persist interspersed within RAD51 filaments; once RAD51 filament assembles, it restricts new RAD52 binding events but RAD52 re-binds after RAD51 dissociation. Single-molecule imaging on ssDNA curtains with purified human RAD52, RPA, and RAD51 The Journal of biological chemistry Medium 28551686
1998 BRCA2 gene product forms in vivo complexes with both RAD51 and p53 in human cells; BRCA2 is a nuclear phosphoprotein, and exogenous BRCA2 expression inhibits p53's transcriptional activity with RAD51 coexpression enhancing this inhibitory effect. Co-immunoprecipitation from cell lysates; transient transfection; p53 transcriptional reporter assays Proceedings of the National Academy of Sciences of the United States of America Medium 9811893

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2010 Purified human BRCA2 stimulates RAD51-mediated recombination. Nature 559 20729832
1998 Rad52 protein stimulates DNA strand exchange by Rad51 and replication protein A. Nature 496 9450760
1998 Catalysis of homologous DNA pairing by yeast Rad51 and Rad54 proteins. Nature 361 9590697
1998 Synergistic actions of Rad51 and Rad52 in recombination and DNA repair. Nature 327 9450758
2018 RPA and RAD51: fork reversal, fork protection, and genome stability. Nature structural & molecular biology 289 29807999
2008 The consequences of Rad51 overexpression for normal and tumor cells. DNA repair 281 18243065
2005 The RAD51 gene family, genetic instability and cancer. Cancer letters 281 15723711
1997 Activities of human recombination protein Rad51. Proceedings of the National Academy of Sciences of the United States of America 229 9012806
1998 The BRCA2 gene product functionally interacts with p53 and RAD51. Proceedings of the National Academy of Sciences of the United States of America 223 9811893
2020 RAD51 Gene Family Structure and Function. Annual review of genetics 191 32663049
2020 RAD51-dependent recruitment of TERRA lncRNA to telomeres through R-loops. Nature 178 33057192
2000 Rad51 accumulation at sites of DNA damage and in postreplicative chromatin. The Journal of cell biology 171 10908572
2004 RAD51-dependent break-induced replication in yeast. Molecular and cellular biology 161 14993274
2000 Evidence for simultaneous protein interactions between human Rad51 paralogs. The Journal of biological chemistry 161 10749867
1997 Rad51 immunocytology in rat and mouse spermatocytes and oocytes. Chromosoma 157 9254722
2003 Gleevec-mediated inhibition of Rad51 expression and enhancement of tumor cell radiosensitivity. Cancer research 143 14612536
2017 RAD51 interconnects between DNA replication, DNA repair and immunity. Nucleic acids research 140 28334891
1997 Elevated recombination in immortal human cells is mediated by HsRAD51 recombinase. Molecular and cellular biology 121 9372947
2015 Rad51 Paralogs Remodel Pre-synaptic Rad51 Filaments to Stimulate Homologous Recombination. Cell 115 26186187
2005 BRCA2 BRC motifs bind RAD51-DNA filaments. Proceedings of the National Academy of Sciences of the United States of America 110 15937124
2018 RAD-ical New Insights into RAD51 Regulation. Genes 105 30551670
2005 RAD51, genomic stability, and tumorigenesis. Cancer letters 101 15670890
2001 Triplex-induced recombination in human cell-free extracts. Dependence on XPA and HsRad51. The Journal of biological chemistry 97 11278954
2004 RAD51 localization and activation following DNA damage. Philosophical transactions of the Royal Society of London. Series B, Biological sciences 94 15065660
2004 Roles of RecA homologues Rad51 and Dmc1 during meiotic recombination. Cytogenetic and genome research 94 15467365
2020 Role of Rad51 and DNA repair in cancer: A molecular perspective. Pharmacology & therapeutics 92 32001312
2018 RADX Modulates RAD51 Activity to Control Replication Fork Protection. Cell reports 84 30021152
2009 Overexpression of RAD51 suppresses recombination defects: a possible mechanism to reverse genomic instability. Nucleic acids research 82 19942681
2014 Rad51 supports triple negative breast cancer metastasis. Oncotarget 80 24811120
2023 RAD51 bypasses the CMG helicase to promote replication fork reversal. Science (New York, N.Y.) 76 37104614
2016 TOPBP1 regulates RAD51 phosphorylation and chromatin loading and determines PARP inhibitor sensitivity. The Journal of cell biology 71 26811421
2007 Rad51 and Rad54 ATPase activities are both required to modulate Rad51-dsDNA filament dynamics. Nucleic acids research 70 17567608
2011 Brca2, Rad51 and Mre11: performing balancing acts on replication forks. DNA repair 69 21900052
2008 Rad51 protein controls Rad52-mediated DNA annealing. The Journal of biological chemistry 69 18337252
2005 Role of recA/RAD51 family proteins in mammals. Acta medica Okayama 69 15902993
2020 RAD51: Beyond the break. Seminars in cell & developmental biology 63 32938550
2020 Regulation and pharmacological targeting of RAD51 in cancer. NAR cancer 62 33015624
1999 Human Rad51 amino acid residues required for Rad52 binding. Journal of molecular biology 61 10448035
2021 HELQ is a dual-function DSB repair enzyme modulated by RPA and RAD51. Nature 59 34937945
2009 Human PSF binds to RAD51 and modulates its homologous-pairing and strand-exchange activities. Nucleic acids research 59 19447914
2010 Single-molecule imaging brings Rad51 nucleoprotein filaments into focus. Trends in cell biology 56 20299221
2023 Centromeres as universal hotspots of DNA breakage, driving RAD51-mediated recombination during quiescence. Molecular cell 55 36702125
2021 Efficient embryonic homozygous gene conversion via RAD51-enhanced interhomolog repair. Cell 55 34043941
2001 Effects of HsRad51 overexpression on cell proliferation, cell cycle progression, and apoptosis. Experimental cell research 50 11461118
2021 Inhibiting homologous recombination by targeting RAD51 protein. Biochimica et biophysica acta. Reviews on cancer 49 34332021
1999 Chlorambucil induction of HsRad51 in B-cell chronic lymphocytic leukemia. Clinical cancer research : an official journal of the American Association for Cancer Research 49 10473103
2017 Human RAD52 interactions with replication protein A and the RAD51 presynaptic complex. The Journal of biological chemistry 48 28551686
2011 Regulation of Rad51 function by phosphorylation. EMBO reports 48 21738226
2021 The RAD51 recombinase protects mitotic chromatin in human cells. Nature communications 47 34508092
2014 HOP2-MND1 modulates RAD51 binding to nucleotides and DNA. Nature communications 44 24943459
2001 Identification and characterisation of a RAD51 gene from Leishmania major. Molecular and biochemical parasitology 43 11420107
2018 BET Inhibition Induces HEXIM1- and RAD51-Dependent Conflicts between Transcription and Replication. Cell reports 42 30463005
2017 Dissociation of Rad51 Presynaptic Complexes and Heteroduplex DNA Joints by Tandem Assemblies of Srs2. Cell reports 42 29241544
2016 FANCI-FANCD2 stabilizes the RAD51-DNA complex by binding RAD51 and protects the 5'-DNA end. Nucleic acids research 41 27694619
2021 Regulation of RAD51 at the Transcriptional and Functional Levels: What Prospects for Cancer Therapy? Cancers 40 34208195
2022 RAD51 protects human cells from transcription-replication conflicts. Molecular cell 39 36002000
2021 Homologous recombination, cancer and the 'RAD51 paradox'. NAR cancer 38 34316706
2021 Mechanisms of distinctive mismatch tolerance between Rad51 and Dmc1 in homologous recombination. Nucleic acids research 37 34871438
2024 RAD51 protects abasic sites to prevent replication fork breakage. Molecular cell 36 39178838
2016 CHK1 and RAD51 activation after DNA damage is regulated via urokinase receptor/TLR4 signaling. Cell death & disease 36 27685627
2021 RAD51 supports DMC1 by inhibiting the SMC5/6 complex during meiosis. The Plant cell 34 34009315
2019 CHD4 regulates the DNA damage response and RAD51 expression in glioblastoma. Scientific reports 34 30872624
1998 Proteolytic cleavage of HsRad51 during apoptosis. FEBS letters 34 9607320
2023 Structural basis for stabilisation of the RAD51 nucleoprotein filament by BRCA2. Nature communications 33 37919288
2021 RADX controls RAD51 filament dynamics to regulate replication fork stability. Molecular cell 32 33453169
2022 TOPORS-mediated RAD51 SUMOylation facilitates homologous recombination repair. Nucleic acids research 31 35061896
2023 BRCA2 chaperones RAD51 to single molecules of RPA-coated ssDNA. Proceedings of the National Academy of Sciences of the United States of America 30 36976771
2020 Rad51 facilitates filament assembly of meiosis-specific Dmc1 recombinase. Proceedings of the National Academy of Sciences of the United States of America 29 32404423
2010 Knockdown of Rad51 expression induces radiation- and chemo-sensitivity in osteosarcoma cells. Medical oncology (Northwood, London, England) 29 20625943
2021 RAD51 paralog function in replicative DNA damage and tolerance. Current opinion in genetics & development 27 34311385
2013 XRCC3 and RAD51 expression are associated with clinical factors in breast cancer. PloS one 27 23977219
2012 RAD51 protein ATP cap regulates nucleoprotein filament stability. The Journal of biological chemistry 27 22275364
1997 Mammalian Rad51 protein: a RecA homologue with pleiotropic functions. Biochimie 27 9466696
2019 Roles of RAD51 and RTEL1 in telomere and rDNA stability in Physcomitrella patens. The Plant journal : for cell and molecular biology 25 30834585
2011 Interactions among Trypanosoma brucei RAD51 paralogues in DNA repair and antigenic variation. Molecular microbiology 25 21615552
2011 Expression and regulation of RAD51 mediate cellular responses to chemotherapeutics. Biochemical pharmacology 25 22222428
2023 FIRRM/C1orf112 is synthetic lethal with PICH and mediates RAD51 dynamics. Cell reports 24 37347663
2023 In vivo tracking of functionally tagged Rad51 unveils a robust strategy of homology search. Nature structural & molecular biology 24 37605042
2022 Cannabidiol inhibits RAD51 and sensitizes glioblastoma to temozolomide in multiple orthotopic tumor models. Neuro-oncology advances 24 35356807
2022 RAD51 paralogs: Expanding roles in replication stress responses and repair. Current opinion in pharmacology 24 36343481
2020 CtBP1 transactivates RAD51 and confers cisplatin resistance to breast cancer cells. Molecular carcinogenesis 24 32124501
2022 Redox regulation of RAD51 Cys319 and homologous recombination by peroxiredoxin 1. Redox biology 23 36058112
2019 Calcitriol Prevents RAD51 Loss and cGAS-STING-IFN Response Triggered by Progerin. Proteomics 23 31834988
2017 A cell-penetrating antibody inhibits human RAD51 via direct binding. Nucleic acids research 23 29036688
2008 Rad51 protein stimulates the branch migration activity of Rad54 protein. The Journal of biological chemistry 23 18617519
2015 RAD51, XRCC3, and XRCC2 mutation screening in Finnish breast cancer families. SpringerPlus 22 25918678
2014 Regulation of Rad51 promoter. Cell cycle (Georgetown, Tex.) 22 24781030
2023 FANCD2 and RAD51 recombinase directly inhibit DNA2 nuclease at stalled replication forks and FANCD2 acts as a novel RAD51 mediator in strand exchange to promote genome stability. Nucleic acids research 21 37526271
2023 Yeast Rad52 is a homodecamer and possesses BRCA2-like bipartite Rad51 binding modes. Nature communications 21 37798272
2023 ssDNA accessibility of Rad51 is regulated by orchestrating multiple RPA dynamics. Nature communications 20 37391417
2020 RADX condenses single-stranded DNA to antagonize RAD51 loading. Nucleic acids research 20 32621611
2018 Spontaneous self-segregation of Rad51 and Dmc1 DNA recombinases within mixed recombinase filaments. The Journal of biological chemistry 20 29382724
2013 The HsRAD51B-HsRAD51C stabilizes the HsRAD51 nucleoprotein filament. DNA repair 20 23810717
2023 Noncanonical Roles of RAD51. Cells 19 37190078
2022 RAD51 is essential for spermatogenesis and male fertility in mice. Cell death discovery 19 35292640
2018 RAD51 and RTEL1 compensate telomere loss in the absence of telomerase. Nucleic acids research 19 29346668
2024 Bleomycin induces senescence and repression of DNA repair via downregulation of Rad51. Molecular medicine (Cambridge, Mass.) 18 38649802
2019 MiR-34s negatively regulate homologous recombination through targeting RAD51. Archives of biochemistry and biophysics 18 30951682
2015 Caffeine inhibits gene conversion by displacing Rad51 from ssDNA. Nucleic acids research 18 26019181
1998 Identification and characterization of the RAD51 gene from the ciliate Tetrahymena thermophila. Nucleic acids research 18 9628914

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