Affinage

RAD52

DNA repair protein RAD52 homolog · UniProt P43351

Length
418 aa
Mass
46.2 kDa
Annotated
2026-06-10
100 papers in source corpus 51 papers cited in narrative 51 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

RAD52 is a ring-forming DNA repair protein that orchestrates homologous recombination (HR) and single-strand annealing through direct DNA binding and protein-mediator activities (PMID:8855248, PMID:9353267, PMID:14765116). Its conserved N-terminal domain forms oligomeric rings that bind ssDNA and catalyze rapid annealing of complementary strands, accelerating annealing thousands-fold over the spontaneous rate (PMID:8855248, PMID:15205482); crystal and cryo-EM structures resolve the mechanism, showing ssDNA wrapped in a positively charged channel around the ring with bases exposed for Watson-Crick pairing, a second DNA-binding site that bridges two rings, and open-ring (rather than closed undecameric) conformations that drive annealing in association with RPA (PMID:30428330, PMID:38658755). As an HR mediator, RAD52 overcomes RPA inhibition of ssDNA by targeting RAD51 to RPA-coated ssDNA to nucleate the presynaptic filament, a function conserved from yeast to human (PMID:9353267, PMID:9450760, PMID:9450758); biochemical and in vivo dissection separates RAD52's presynaptic RAD51-loading role from its DNA-binding-dependent second-end capture and annealing role, and from a RAD51-interaction-dependent role in protecting RAD51 filaments against the Srs2 translocase (PMID:14765116, PMID:19812039, PMID:29985128). RAD52 catalyzes second-end capture of the displaced strand from a RAD51-generated D-loop on RPA-coated ssDNA, coupling annealing to repair synthesis by polymerase eta (PMID:17093500, PMID:18313388), and uniquely performs inverse strand exchange using RNA as template to enable RNA-templated and transcription-associated DSB repair, being recruited to breaks via DNA:RNA hybrids and processing R-loops with XPG (PMID:28602639, PMID:30245011). At the replication interface, RAD52 marks stalled and collapsed forks, promotes their restart, limits excessive end resection by competing with Sgs1/Rqh1, and prevents pathological SMARCAL1-driven fork reversal and MRE11-dependent fork degradation (PMID:27984746, PMID:30926821, PMID:31542296); in mitosis it drives MiDAS at common fragile sites by recruiting MUS81 and POLD3, and supports break-induced replication at telomeres (PMID:27984745, PMID:31777915). RAD52 defines an alternative HR pathway that is synthetically lethal with BRCA2 deficiency (PMID:21148102). Its activities are gated by SUMOylation, which inhibits DNA binding and annealing and biases pathway choice from single-strand annealing toward gene conversion, by cell-cycle-coupled phosphorylation, and by partner proteins including DSS1, which remodel its oligomeric conformation (PMID:20371517, PMID:31799622, PMID:16707661).

Mechanistic history

Synthesis pass · year-by-year structured walk · 13 steps
  1. 1996 High

    Established RAD52's intrinsic biochemical activity, answering whether it acts directly on DNA: it binds ssDNA/dsDNA and dramatically accelerates annealing of complementary strands.

    Evidence Recombinant yeast Rad52, DNA binding and annealing kinetics, N-terminal domain mapping

    PMID:8855248

    Open questions at the time
    • Did not resolve how the N-terminal domain contacts DNA structurally
    • No partner-protein context
  2. 1998 High

    Defined RAD52 as an HR mediator and showed the function is conserved to humans, answering how RAD51 overcomes RPA inhibition of ssDNA: RAD52 targets RAD51 to RPA-ssDNA to restore strand exchange.

    Evidence In vitro strand exchange and presynaptic filament assays with purified yeast and human RAD51, RPA, RAD52

    PMID:9353267 PMID:9450758 PMID:9450759 PMID:9450760

    Open questions at the time
    • Precise protein-protein interface not mapped
    • In vivo timing of mediator action unresolved
  3. 1998 High

    Provided the structural and partner framework: RAD52 forms multimeric rings, binds DSB ends protecting them from nucleases, and physically engages RPA species-specifically and in vivo co-assembles with RPA in DSB-dependent foci.

    Evidence Electron microscopy, nuclease protection, two-hybrid with RPA subunits, meiotic immunostaining/epistasis

    PMID:10227297 PMID:9619627 PMID:9632824 PMID:9679065

    Open questions at the time
    • Ring stoichiometry not yet defined
    • Functional consequence of distinct RPA subunit contacts unresolved
  4. 2001 High

    Linked RAD52 dynamics to replication and revealed a RAD51-independent activity: foci form in S phase upon DSBs, and an N-terminal fragment defective in RAD51 binding still catalyzes homologous pairing.

    Evidence Live-cell GFP imaging with replication/checkpoint mutants; in vitro pairing with truncation mutants and EM

    PMID:11454867 PMID:11459964 PMID:11571269

    Open questions at the time
    • In vivo relevance of RAD51-independent pairing not established
    • Mechanism coupling foci to replication unresolved
  5. 2004 High

    Dissected RAD52's distinct presynaptic, synaptic, and postsynaptic roles in vivo and mapped strand-exchange activity to the ring-forming N-terminal domain.

    Evidence HO-induced DSB time-course IF/ChIP, biochemical ssDNA complexes, in vitro strand exchange with truncations

    PMID:14765116 PMID:15205482

    Open questions at the time
    • Postsynaptic mechanism not biochemically reconstituted
    • AT-content dependence mechanism unexplained
  6. 2006 High

    Defined RAD52's role in second-end capture, answering how the displaced D-loop strand is annealed: RAD52 anneals RPA-coated ssDNA following RAD51-mediated D-loop formation.

    Evidence In vitro strand exchange plus second-end capture with purified proteins and recombination-deficient RPA mutant

    PMID:17093500

    Open questions at the time
    • Coupling to repair synthesis not yet shown
    • Regulation of capture timing unresolved
  7. 2008 High

    Resolved the structural basis of annealing and pathway channeling: a second DNA-binding site enables ternary ssDNA-dsDNA complexes and D-loop formation, while RAD51 filaments inhibit RAD52 annealing in an ATP-dependent manner.

    Evidence Structure-based alanine scanning, D-loop/supercoiling assays, ssDNA annealing with RAD51/RAD59

    PMID:16565518 PMID:18337252 PMID:18593704

    Open questions at the time
    • How channeling is regulated in vivo not established
    • Second-site contribution to in vivo HR untested in some contexts
  8. 2009 High

    Established separation-of-function: the N-terminal DNA-binding domain is needed for second-end capture but not RAD51 delivery; recruitment requires CDK1 and is restrained by Mec1/Tel1 checkpoint kinase, and SUMOylation/phosphorylation regulate activity.

    Evidence rad52-R70A mutant biochemistry/ChIP, live-cell imaging with CDK1/Mec1 mutants, SUMOylation assays

    PMID:16707661 PMID:19262568 PMID:19530647 PMID:19812039 PMID:20371517

    Open questions at the time
    • Site-specific phosphorylation consequences not fully mapped
    • Interplay between SUMO and phospho regulation unresolved
  9. 2010 High

    Defined RAD52 as an alternative HR mediator and resolved its concentration-dependent ssDNA binding modes underlying annealing.

    Evidence BRCA2 synthetic lethality by siRNA with HR/focus readouts; single-molecule FRET with RPA-interaction mutants

    PMID:20081207 PMID:21148102

    Open questions at the time
    • Therapeutic window of BRCA2-RAD52 synthetic lethality not defined here
    • Structural basis of mode switching unresolved at the time
  10. 2017 High

    Uncovered RNA-templated repair: RAD52 catalyzes inverse strand exchange using RNA as template and is recruited to breaks via DNA:RNA hybrids to drive transcription-associated HR with XPG, including in post-mitotic neurons.

    Evidence In vitro inverse strand exchange with RNA, in vivo RNA-templated repair, RNA-hybrid recruitment and pathway-choice assays

    PMID:28602639 PMID:29217771 PMID:30245011

    Open questions at the time
    • How RAD52 discriminates RNA template specificity unclear
    • In vivo contribution of RNA-templated repair to genome stability not quantified
  11. 2019 High

    Placed RAD52 at the replication fork as a gatekeeper, answering how forks are protected: it limits resection by competing with Sgs1/Rqh1 and prevents excessive SMARCAL1-mediated reversal and MRE11 degradation.

    Evidence In vivo resection assays in two yeast species, single-molecule competition, siRNA/inhibitor DNA fiber and fork-binding/SMARCAL1 assays

    PMID:27984746 PMID:30926821 PMID:31542296

    Open questions at the time
    • Molecular basis of fork occlusion not structurally defined
    • Coordination between resection control and HR initiation unresolved
  12. 2016 High

    Defined RAD52's mitotic and telomeric replication-stress roles: it drives MiDAS at common fragile sites by recruiting MUS81/POLD3 and supports break-induced replication at telomeres independent of RAD51/BRCA2.

    Evidence siRNA/CRISPR knockout, EdU MiDAS assays, MUS81/POLD3 recruitment IF, telomere synthesis and BIR assays with R-loop dependency

    PMID:27984745 PMID:30692206 PMID:31777915

    Open questions at the time
    • Mechanism of selective MUS81/POLD3 recruitment unresolved
    • How RAD52 is targeted to specific fragile/telomeric loci unclear
  13. 2024 High

    Delivered high-resolution mechanism: cryo-EM and crystallography show open-ring RAD52 (not closed undecamers) drives annealing in a charged channel, with defined ssDNA wrapped/trapped conformations and an RPA2-winged-helix contact at the ring opening.

    Evidence Cryo-EM and X-ray structures of RAD52-ssDNA and RAD52-RPA intermediates, biochemical annealing, domain mutagenesis

    PMID:30428330 PMID:37798272 PMID:38658755

    Open questions at the time
    • Structures of the RAD51-mediator complex not resolved here
    • Conformational transitions during second-end capture not visualized

Open questions

Synthesis pass · forward-looking unresolved questions
  • How RAD52's many regulated activities (mediator loading, annealing, fork protection, RNA-templated repair, MiDAS) are coordinated and selected in vivo, and how its modifications integrate to govern pathway choice, remains unresolved.
  • No unified model of in vivo activity selection
  • Regulatory integration of SUMO/phospho and partner binding incomplete
  • Structural basis of the RAD51-loading mediator step undefined

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0003677 DNA binding 6 GO:0060090 molecular adaptor activity 4 GO:0098772 molecular function regulator activity 4 GO:0003723 RNA binding 1 GO:0140098 catalytic activity, acting on RNA 1
Localization
GO:0005654 nucleoplasm 3 GO:0005634 nucleus 2
Pathway
R-HSA-73894 DNA Repair 5 R-HSA-69306 DNA Replication 4 R-HSA-8953897 Cellular responses to stimuli 3
Partners
DSS1MUS81OGG1POLD3RAD51RAD59RPAXPG
Complex memberships
PALB2-RAD52 complexRAD51-RAD52-RPA presynaptic complexRAD52-RAD59 complex

Evidence

Reading pass · 51 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1996 Yeast Rad52 protein directly binds both single-stranded and double-stranded DNA and stimulates annealing of complementary ssDNA at a rate 3500-fold faster than spontaneous annealing; the DNA binding domain was mapped to the evolutionarily conserved N-terminus. Recombinant protein purification, DNA binding assays, DNA annealing kinetics assay Proceedings of the National Academy of Sciences of the United States of America High 8855248
1997 Yeast Rad52 functions as a mediator (co-factor) for Rad51 recombinase by overcoming the inhibitory effect of RPA on ssDNA, restoring efficient DNA strand exchange when Rad51 and RPA are added simultaneously to ssDNA. In vitro DNA strand exchange assay with purified yeast Rad51, RPA, and Rad52 proteins The Journal of biological chemistry High 9353267
1998 Yeast Rad52 stimulates Rad51-mediated DNA strand exchange by targeting Rad51 to RPA-ssDNA complexes (overcoming RPA inhibition); stimulation requires concerted action of both Rad51 and RPA, implying specific protein-protein interactions between Rad52, Rad51, and RPA. In vitro DNA strand exchange assay, presynaptic filament formation assay with purified proteins Nature High 9450760
1998 Yeast Rad52 stimulates Rad51 strand exchange and nucleoprotein filament formation; binding to Rad51 is necessary for this stimulatory effect. In vitro strand exchange assay, protein-protein interaction studies, nucleoprotein filament formation assay Nature High 9450759
1998 Human Rad52 stimulates homologous pairing by human Rad51, indicating the Rad52–Rad51 functional relationship is conserved in humans; hRad52 DNA binding properties indicate involvement in an early stage of Rad51-mediated recombination. In vitro homologous pairing assay with purified human Rad51 and Rad52 proteins Nature High 9450758
1998 Yeast Rad52 forms multimeric ring structures as observed by electron microscopy; it binds ssDNA and interacts physically with RPA (specifically RPA enhances ssDNA annealing); this enhancement is species-specific (E. coli SSB and T4 gp32 do not substitute). Electron microscopy, ssDNA annealing assay, protein-protein interaction (binding assays) Genes to cells : devoted to molecular & cellular mechanisms High 9619627
1998 Rad52 physically interacts with all three subunits of yeast RPA (two-hybrid analysis); mutations in the amino-terminal DNA-binding domain of Rad52 disrupt interaction with Rad51 and with the large RPA subunit (Rfa1) but retain self-interaction and interaction with Rfa2; RAD52 and RFA1 are in the same genetic epistasis pathway. Yeast two-hybrid assay, genetic epistasis analysis Molecular and cellular biology Medium 9632824
1998 In meiosis, Rad52 and RPA co-assemble into cytologically detectable subnuclear foci; Rad52 foci are distinct from Rad51/Dmc1 foci and require DSBs (Spo11-dependent); Rad52, Rad55, and Rad57 are all required for Rad51 focus formation, supporting a model in which they collectively promote strand exchange complex assembly. Immunostaining, colocalization microscopy, genetic epistasis (spo11 mutant, ionizing radiation rescue) Genes & development High 9679065
1999 Human Rad52 binds directly to DNA double-strand breaks, protects them from exonuclease attack, and facilitates end-to-end DNA interactions, consistent with an early role in DSB repair by homologous recombination. In vitro DNA binding assay, nuclease protection assay, electron microscopy Nature High 10227297
2000 Human RAD52 binds ssDNA and tailed duplex DNA via precise interactions with the terminal nucleotide base; hydroxyl radical footprinting revealed a 4-nucleotide repeat hypersensitivity pattern phased from the DNA terminus over ~36 nucleotides. Hydroxyl radical footprinting, nuclease protection assay, in vitro DNA binding The EMBO journal High 10921897
2001 Rad52-GFP relocalizes from a diffuse nuclear distribution to distinct foci upon DNA double-strand break induction (gamma-irradiation, meiosis, HO endonuclease); foci form almost exclusively during S phase of mitotic cells, and their frequency increases in replication (pol12-100) and checkpoint (mec1) mutants, indicating coordination with DNA replication. Live-cell fluorescence microscopy (GFP fusion), genetic analysis with replication/checkpoint mutants, DSB induction assays Proceedings of the National Academy of Sciences of the United States of America High 11459964
2001 Human Rad52 promotes homologous pairing via a presynaptic complex with ssDNA; an N-terminal fragment (residues 1–237) defective in Rad51 binding still catalyzes homologous pairing, forming nucleoprotein filaments with ssDNA, indicating a Rad51-independent recombination function. In vitro homologous pairing assay, electron microscopy, truncation mutagenesis The Journal of biological chemistry High 11454867
2001 Human RAD52 promotes single-strand annealing (SSA) in vitro; electron microscopy visualized specific binding of multiple RAD52 rings to resected DSB termini and large protein complexes at heteroduplex joints, defining intermediates of RAD52-mediated annealing. In vitro SSA assay, electron microscopy of reaction intermediates EMBO reports High 11571269
2003 Yeast Rad52 binds preferentially to ssDNA rather than to free DNA ends (in contrast to Ku which binds free ends); Rad52 aggregates different ssDNAs in close proximity independently of DNA ends or extensive sequence complementarity. In vitro DNA binding assay with defined substrates, comparison with Ku protein Nucleic acids research Medium 12954758
2004 In vivo, Rad52 plays three distinct roles during homologous recombination: a presynaptic role necessary for Rad51 assembly at a DSB, a synaptic role with Rad51 filaments, and a postsynaptic role after Rad51 dissociates; ssDNA complexes containing both Rad51 and Rad52 were identified biochemically. Immunofluorescence during HO-induced DSB repair (time-course), chromatin immunoprecipitation, biochemical ssDNA complex analysis The EMBO journal High 14765116
2004 Human and yeast Rad52 proteins promote DNA strand exchange in vitro; this activity resides in the N-terminal domain (residues 1–237 for human Rad52) that forms rings; strand exchange yield is proportional to AT content. In vitro DNA strand exchange assay, N-terminal truncation analysis Proceedings of the National Academy of Sciences of the United States of America Medium 15205482
2005 Saturating alanine-scanning mutagenesis of the N-terminal domain of full-length human Rad52 identified residues (within the first 85 residues) involved in direct ssDNA contact; these residues map to the DNA binding channel observed in crystal structures of truncation mutants. Alanine-scanning mutagenesis, in vitro DNA binding assay Journal of molecular biology Medium 15571718
2006 Rad52 promotes annealing of the displaced ssDNA strand from a Rad51-mediated D-loop (second ssDNA capture/second-end capture), acting on RPA-coated ssDNA; RPA-rfa1-t11 (recombination-deficient RPA) fails to support this annealing, explaining its in vivo phenotype. E. coli RecO/SSB are functional analogs, demonstrating the conserved nature of this step. In vitro DNA strand exchange + second-strand capture assay with purified proteins, mutant RPA analysis The EMBO journal High 17093500
2006 Yeast Rad59 can anneal complementary ssDNA but cannot anneal RPA-coated ssDNA (unlike Rad52), follows first-order kinetics (versus second-order for Rad52), and enhances Rad52-mediated annealing at elevated salt; these biochemical differences distinguish their recombinational roles. Quantitative in vitro ssDNA annealing assay with RPA, kinetics analysis The Journal of biological chemistry High 16565518
2008 DNA repair synthesis catalyzed by human DNA polymerase eta (pol eta) acting on the priming strand of a D-loop promotes RAD52-dependent second-end capture and annealing; pol delta and pol iota cannot substitute for pol eta; RAD52 cannot be replaced by RAD51; RPA (but not E. coli SSB) stimulates the reaction. In vitro second-end capture assay with purified human proteins, defined polymerase substitution Molecular cell High 18313388
2008 Human Rad52 has a second DNA binding site identified by structure-based alanine scan mutagenesis; this site enables the Rad52-ssDNA complex to form a ternary complex with dsDNA; mutations in this site impair D-loop formation and abolish Rad52-induced positive supercoiling of dsDNA. Structure-based alanine-scanning mutagenesis, D-loop formation assay, supercoiling assay The Journal of biological chemistry High 18593704
2008 Yeast Rad51 prevents Rad52-mediated ssDNA annealing in an ATP-dependent manner via specific Rad51–Rad52 protein–protein interaction; the Rad51 nucleoprotein filament is more inhibitory than free Rad51; Rad59 partially restores annealing in the presence of Rad51, suggesting coordinated channeling between strand invasion and annealing pathways. In vitro ssDNA annealing assay, ATP dependence analysis, protein-protein interaction study The Journal of biological chemistry High 18337252
2009 The Rad52 amino-terminal DNA binding domain is required for DNA annealing (second-end capture) but not for Rad51 delivery to DSBs; rad52-R70A (compromised DNA binding) associates with DSBs and recruits Rad51 normally but cannot complete recombination due to failure in second-end capture. Purified mutant protein biochemical assay (annealing), chromatin immunoprecipitation (ChIP) at DSBs, genetic analysis of recombination intermediates The Journal of biological chemistry High 19812039
2009 Phosphorylated human RPA promotes formation of a complex with monomeric Rad52 and causes transfer of ssDNA from RPA to Rad52, suggesting RPA phosphorylation regulates the mediator function of Rad52 in the first steps of DSB repair. Analytical SEC-MALS, UV crosslinking to identify ssDNA-bound partner, SDS-PAGE/Western analysis Biochemistry Medium 19530647
2009 Srs2 helicase evicts Rad52 from RPA-ssDNA during translocation, promoting rapid redistribution of both Rad52 and RPA, thereby resolving potentially pathogenic nucleoprotein intermediates. Single-molecule fluorescence imaging of Srs2 acting on ssDNA curtains coated with RPA and Rad52 Cell reports Medium 29045827
2009 Rad52-RPA interaction requires multiple RPA molecules associated with ssDNA (cooperative contacts); Rad51 inhibits Rad52-promoted ssDNA aggregation and subsequent annealing; after DNA strand invasion, Rad51-dsDNA complex disrupts Rad52-RPA interaction on ssDNA, limiting illegitimate second-end capture. In vitro DNA annealing assay, protein-protein interaction biochemistry with mutant RPA Journal of molecular biology Medium 19445949
2009 Rad52 recruitment to DSB sites requires B-type cyclin/CDK1 (Cdc28) activity; during intra-S-phase checkpoint (hydroxyurea), Mec1/Tel1 kinase inhibits Rad52 focus formation at both DSBs and stalled replication forks; Rad52 foci colocalize with PCNA foci. Live-cell fluorescence microscopy (Rad52-GFP), genetic analysis with CDK1/Mec1 mutants, co-localization with PCNA-GFP The EMBO journal High 19262568
2010 Rad52 SUMOylation inhibits its DNA binding and ssDNA annealing activities in vitro; SUMOylation is enhanced by ssDNA; in vivo, SUMO-deficient Rad52 mutants show longer focus duration and a shift from single-strand annealing toward gene conversion during spontaneous mitotic recombination. In vitro SUMOylation assay, DNA binding assay, ssDNA annealing assay with SUMOylated Rad52, in vivo recombination assays, live-cell microscopy Nucleic acids research High 20371517
2010 Human RAD52 binds ssDNA in two concentration-dependent modes: at low protein concentration ssDNA is wrapped around the ring circumference (promoting efficient annealing), while at higher concentrations ssDNA is stretched between multiple rings; annealing via two RAD52-ssDNA complexes (one per complementary strand); hRad52 mutants impaired in hRPA binding (RQK/AAA and 1-212) compete with RPA for ssDNA and fail to counteract RPA-mediated duplex destabilization. Single-molecule FRET, fluorescence-based DNA annealing assay, RPA interaction mutant analysis Nucleic acids research High 20081207
2010 Loss of Rad52 is synthetically lethal with BRCA2 deficiency; Rad52 depletion in BRCA2-deficient cells reduces spontaneous and DSB-induced homologous recombination and Rad51 focus formation; Rad52-Rad51 foci form independently of BRCA2, defining Rad52 as an alternative HR mediator pathway. siRNA knockdown, HR frequency assay, Rad51 focus formation assay, chromosome aberration analysis Proceedings of the National Academy of Sciences of the United States of America High 21148102
2016 Human RAD52 is required for Mitotic DNA Synthesis (MiDAS) at common fragile sites (CFSs); RAD52 is required for timely recruitment of MUS81 and POLD3 to CFSs in early mitosis; RAD51 and BRCA2 are dispensable for MiDAS but required to counteract replication stress at CFSs during S-phase. siRNA knockdown, EdU incorporation (MiDAS assay), immunofluorescence for MUS81/POLD3 recruitment, epistasis analysis Molecular cell High 27984745
2016 Mammalian RAD52 localizes to collapsed replication fork foci induced by oncogenes or chemicals; siRNA depletion or CRISPR/Cas9 knockout of RAD52 compromises restart of collapsed replication forks and leads to DNA damage under replication stress conditions. siRNA knockdown, CRISPR/Cas9 knockout, immunofluorescence (focus formation), replication fork restart assay (DNA fiber analysis), oncogene overexpression model Molecular cell High 27984746
2017 Yeast and human Rad52 catalyze inverse strand exchange: Rad52 forms a complex with dsDNA and promotes strand exchange with homologous ssRNA or ssDNA; this activity is specific to Rad52 (not Rad51 or Rad59); inverse strand exchange with RNA contributes to RNA-templated DSB repair in yeast. In vitro inverse strand exchange assay with purified proteins and RNA substrates, in vivo RNA-templated DSB repair assay in yeast Molecular cell High 28602639
2017 Human RAD52 is recruited to DSB sites in a DNA:RNA hybrid-dependent manner and promotes XPG-mediated R-loop processing to initiate transcription-associated homologous recombination repair (TA-HRR); loss of TA-HRR due to RAD52 dysfunction redirects DSB repair to NHEJ, increasing genomic aberrations. siRNA knockdown, DNA:RNA hybrid-dependent recruitment assay (IF), XPG interaction analysis, NHEJ/HR pathway choice assay Cell High 30245011
2017 Human RAD52 is required for RNA-templated DSB repair in post-mitotic neurons; RAD52 is recruited to DSBs in a nascent mRNA-dependent manner; recruitment is reduced by transcription inhibition; amyloid-β inhibits RAD52 expression and DNA damage response. Immunofluorescence in differentiated neurons, transcription inhibitor treatment, RAD52 focus formation assay The Journal of biological chemistry Medium 29217771
2017 Human RAD52 binds tightly to RPA-coated ssDNA using single-molecule imaging; RAD52 imparts an inhibitory effect on RPA turnover; during presynaptic complex assembly, most RAD52 and RPA are displaced by RAD51, but some RAD52-RPA clusters persist; once RAD51 dissociates, new RAD52 binding occurs on ssDNA. Single-molecule imaging (ssDNA curtains), total internal reflection fluorescence microscopy The Journal of biological chemistry High 28551686
2018 RAD52 Rad51-association is essential for protecting Rad51 filaments against dissociation by the Srs2 DNA translocase, but the Rad52–Rad51 interaction is not required for Rad51 filament formation per se (mutations disrupting Rad52-Rad51 interaction do not affect gene conversion or Rad51 filament formation in vivo). Rad52 point mutations disrupting Rad51 interaction, in vivo gene conversion assay, in vitro and in vivo Rad51 filament formation analysis, Srs2 antirecombination assay eLife High 29985128
2019 RAD52 prevents excessive remodeling of stalled replication forks by binding to the fork, promoting its occlusion, and counteracting SMARCAL1 loading; loss of RAD52 leads to excessive MRE11-mediated degradation of reversed replication forks, slightly defective replication restart, and chromosome instability. siRNA knockdown, small-molecule RAD52 inhibitor, DNA fiber analysis, in vitro fork binding assay, SMARCAL1 loading assay (ChIP/IF) Nature communications High 30926821
2019 Yeast Rad52 limits extensive DNA end resection at DSBs: in rad52 mutant cells, resection rate increases from ~3–5 kb/h to ~10–20 kb/h in an Rqh1 (fission yeast)/Sgs1 (budding yeast)-dependent manner; in vitro, Rad52 competes with Sgs1 for DNA end binding and inhibits Sgs1 translocation along DNA. In vivo resection assay (Southern blot/qPCR in fission and budding yeast), genetic epistasis, single-molecule analysis with purified proteins Molecular cell High 31542296
2019 RAD52 deficiency reduces spontaneous telomeric DNA synthesis and replication stress-associated recombination in G2 (ALT pathway); RAD52 is dispensable for DSB-induced telomere synthesis; combined loss of RAD52 and SLX4 results in elevated telomere loss and unresolved recombination intermediates (epistasis distinct from RAD52 alone). RAD52 knockout (CRISPR), telomere synthesis assay (EdU at telomeres), CRISPR screen for SLX4 synthetic lethality, telomere FISH Genes & development High 30692206
2020 ROS-induced telomeric DSBs trigger R-loop accumulation (TERRA- and TRF2-dependent); RAD52 is recruited to telomeric R-loops through interactions with both CSB and DNA:RNA hybrids; RAD52 is required for efficient repair of telomeric DSBs through recruitment of POLD3 for break-induced replication (BIR); RAD52 function in telomere repair requires its ability to bind POLD3. siRNA knockdown, immunofluorescence colocalization, RNaseH1 treatment (R-loop dependency), co-immunoprecipitation (RAD52-CSB, RAD52-POLD3), DNA fiber/BIR assay Nucleic acids research High 31777915
2020 Rad52 liquid droplets at DNA damage sites fuse into a repair centre droplet via petite DIMs (damage-inducible intranuclear microtubule filaments); the larger droplet concentrates tubulin and projects aster-DIMs that tether the repair centre to longer DIMs mediating mobilization of damaged DNA to the nuclear periphery. Live-cell fluorescence microscopy (Rad52-GFP), genetic disruption of DIM formation, liquid droplet fusion imaging Nature communications Medium 32019927
2020 Rad52 (but not Rad51/Rad57) facilitates DNA damage tolerance through a non-recombinogenic mechanism by acting with the TLS machinery (Rad6/Rad18-mediated PCNA ubiquitylation and polymerases Rev1/Pol ζ); Rad52 (along with Rad51 and Rad57) also facilitates Rad6/Rad18 binding to chromatin and DNA damage-induced PCNA ubiquitylation. Genetic epistasis (rad52, rad54, rad51, rad57 mutants), mutagenesis assay, PCNA ubiquitylation assay (Western blot/ChIP) EMBO reports Medium 33289333
2020 DSS1 interacts with RAD52 and stimulates its activities: DSS1 binding changes RAD52 oligomeric conformation, modulates DNA binding, stimulates single-strand annealing, and promotes strand invasion. Co-immunoprecipitation, in vitro SSA assay, strand invasion assay, oligomeric state analysis Nucleic acids research Medium 31799622
2021 BRCA1-RNAi protein complex generates damage-associated small RNAs (sdRNAs) that promote DSB repair via the PALB2-RAD52 complex at transcriptional termination pause sites containing R-loops and ssDNA breaks; this sdRNA repair operates in both quiescent and proliferating cells. siRNA/shRNA knockdown, co-immunoprecipitation (PALB2-RAD52 interaction), dsRNA-repair assay, cell-cycle specific readouts Nature Medium 33536619
2023 Yeast Rad52 is a homodecameric ring with intrinsic structural asymmetry; each subunit has an ordered N-terminal and disordered C-terminal half; the C-terminus contains two conserved charged patches harboring Rad51-interacting and RPA-interacting motifs; Rad51 interacts with Rad52 at two sites (within the disordered C-terminus and in the ordered ring); interactions between these patches regulate ssDNA binding. Single-particle cryo-electron microscopy, biophysical interaction assays (ITC, SEC), mutagenesis of charged patches Nature communications High 37798272
2018 Crystal structures of human RAD52 in complex with ssDNA revealed two conformations: a 'wrapped' conformation where ssDNA encircles the ring with bases exposed for Watson-Crick pairing, and a 'trapped' conformation where ssDNA is bound between two RAD52 rings via the second DNA binding site, providing a structural framework for the annealing mechanism. X-ray crystallography of human RAD52-ssDNA complexes iScience High 30428330
2024 Cryo-EM and biochemical analyses revealed that ssDNA annealing is driven by RAD52 open rings (not the closed undecameric rings), in association with RPA; ssDNA sits in a positively charged channel around the ring; annealing is driven by the N-terminal domains; C-terminal regions modulate open-ring conformation and RPA interaction; RPA associates at the ring-opening site via interactions between the RAD52 RPA-interacting domain and the winged-helix domain of RPA2. Cryo-electron microscopy (structural snapshots throughout annealing), biochemical annealing assays, domain mutagenesis Nature High 38658755
2006 Rad52 phosphorylation occurs both in a cell cycle-independent and a cell cycle-dependent manner; phosphorylation requires the C-terminus of Rad52 but not its interaction with Rad51; multiple translation start sites also generate discrete Rad52 protein species. Protein-blot analysis, start-codon mutant analysis, cell cycle synchronization, Rad52 domain truncation analysis Nucleic acids research Medium 16707661
2009 Rad52 interacts with OGG1 (base excision repair glycosylase) in vitro and in vivo; OGG1 inhibits Rad52 catalytic activities while Rad52 stimulates OGG1 incision activity (likely increasing turnover); Rad52 co-localizes with OGG1 after oxidative stress but not after ionizing radiation; RAD52-depleted human/mouse cells show increased sensitivity to oxidative stress and higher accumulation of oxidized bases. Co-immunoprecipitation, in vitro activity assays (OGG1 incision, Rad52 annealing), siRNA knockdown, KO mouse cells, immunofluorescence colocalization Molecular and cellular biology High 19506022
2003 Yeast Rad52 forms a complex with Rad51 and RPA, and also a Rad52-Rad59 complex; Rad52 is required for Rad51-Rad52-Rad59 and RPA-Rad52-Rad59 complex formation; the N-terminal self-interaction domain is required for Rad59 binding; Rad52-Rad59 participates in single-strand annealing, while Rad51-Rad52-Rad59 in gene conversion. Co-immunoprecipitation, two-hybrid assay, domain truncation analysis DNA repair Medium 13679150

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2002 Role of RAD52 epistasis group genes in homologous recombination and double-strand break repair. Microbiology and molecular biology reviews : MMBR 825 12456786
1998 Rad52 protein stimulates DNA strand exchange by Rad51 and replication protein A. Nature 496 9450760
1997 Function of yeast Rad52 protein as a mediator between replication protein A and the Rad51 recombinase. The Journal of biological chemistry 468 9353267
1996 DNA strand annealing is promoted by the yeast Rad52 protein. Proceedings of the National Academy of Sciences of the United States of America 397 8855248
1998 Stimulation by Rad52 of yeast Rad51-mediated recombination. Nature 392 9450759
2001 Rad52 forms DNA repair and recombination centers during S phase. Proceedings of the National Academy of Sciences of the United States of America 374 11459964
1998 Synergistic actions of Rad51 and Rad52 in recombination and DNA repair. Nature 327 9450758
2016 RAD52 Facilitates Mitotic DNA Synthesis Following Replication Stress. Molecular cell 318 27984745
2010 Rad52 inactivation is synthetically lethal with BRCA2 deficiency. Proceedings of the National Academy of Sciences of the United States of America 288 21148102
2018 Human Rad52 Promotes XPG-Mediated R-loop Processing to Initiate Transcription-Associated Homologous Recombination Repair. Cell 268 30245011
1999 Binding of double-strand breaks in DNA by human Rad52 protein. Nature 254 10227297
1998 Rad52 forms ring structures and co-operates with RPA in single-strand DNA annealing. Genes to cells : devoted to molecular & cellular mechanisms 241 9619627
1998 Rad52 associates with RPA and functions with rad55 and rad57 to assemble meiotic recombination complexes. Genes & development 228 9679065
2016 Mammalian RAD52 Functions in Break-Induced Replication Repair of Collapsed DNA Replication Forks. Molecular cell 212 27984746
1980 Effects of the RAD52 Gene on Recombination in SACCHAROMYCES CEREVISIAE. Genetics 196 17248995
2020 DNA repair by Rad52 liquid droplets. Nature communications 139 32019927
2001 Homologous pairing promoted by the human Rad52 protein. The Journal of biological chemistry 135 11454867
1998 Studies of the interaction between Rad52 protein and the yeast single-stranded DNA binding protein RPA. Molecular and cellular biology 123 9632824
2010 Human Rad52 binds and wraps single-stranded DNA and mediates annealing via two hRad52-ssDNA complexes. Nucleic acids research 118 20081207
2017 Rad52 Inverse Strand Exchange Drives RNA-Templated DNA Double-Strand Break Repair. Molecular cell 113 28602639
2008 DNA repair synthesis facilitates RAD52-mediated second-end capture during DSB repair. Molecular cell 103 18313388
2004 In vivo assembly and disassembly of Rad51 and Rad52 complexes during double-strand break repair. The EMBO journal 102 14765116
1998 Visualisation of human rad52 protein and its complexes with hRad51 and DNA. Journal of molecular biology 100 9837724
2019 RAD52 and SLX4 act nonepistatically to ensure telomere stability during alternative telomere lengthening. Genes & development 98 30692206
2006 Rad52-mediated DNA annealing after Rad51-mediated DNA strand exchange promotes second ssDNA capture. The EMBO journal 96 17093500
2017 Ectopic expression of RAD52 and dn53BP1 improves homology-directed repair during CRISPR-Cas9 genome editing. Nature biomedical engineering 91 31015609
2012 Molecular pathways: understanding the role of Rad52 in homologous recombination for therapeutic advancement. Clinical cancer research : an official journal of the American Association for Cancer Research 91 23071261
2017 RAD52 is required for RNA-templated recombination repair in post-mitotic neurons. The Journal of biological chemistry 86 29217771
2016 Targeting BRCA1- and BRCA2-deficient cells with RAD52 small molecule inhibitors. Nucleic acids research 84 26873923
2020 An R-loop-initiated CSB-RAD52-POLD3 pathway suppresses ROS-induced telomeric DNA breaks. Nucleic acids research 80 31777915
2010 Rad52 SUMOylation affects the efficiency of the DNA repair. Nucleic acids research 80 20371517
2018 p53 orchestrates DNA replication restart homeostasis by suppressing mutagenic RAD52 and POLθ pathways. eLife 79 29334356
2019 Rad52 prevents excessive replication fork reversal and protects from nascent strand degradation. Nature communications 77 30926821
1997 The RAD52 epistasis group in mammalian double strand break repair. Seminars in immunology 77 9200329
2018 Simultaneous Targeting of PARP1 and RAD52 Triggers Dual Synthetic Lethality in BRCA-Deficient Tumor Cells. Cell reports 76 29898385
2000 Coordinated response of mammalian Rad51 and Rad52 to DNA damage. EMBO reports 75 11256631
2015 Small-Molecule Disruption of RAD52 Rings as a Mechanism for Precision Medicine in BRCA-Deficient Cancers. Chemistry & biology 73 26548611
2016 Reappearance from Obscurity: Mammalian Rad52 in Homologous Recombination. Genes 70 27649245
2008 Identification of a second DNA binding site in the human Rad52 protein. The Journal of biological chemistry 70 18593704
2008 Rad51 protein controls Rad52-mediated DNA annealing. The Journal of biological chemistry 69 18337252
2000 Precise binding of single-stranded DNA termini by human RAD52 protein. The EMBO journal 69 10921897
2019 Distinct roles of RAD52 and POLQ in chromosomal break repair and replication stress response. PLoS genetics 65 31381562
2004 Suppression of retroviral infection by the RAD52 DNA repair protein. The EMBO journal 64 15297876
1983 Isolation and characterization of yeast DNA repair genes : I. Cloning of the RAD52 gene. Current genetics 64 24173148
2006 DNA annealing mediated by Rad52 and Rad59 proteins. The Journal of biological chemistry 62 16565518
2001 Visualization of recombination intermediates produced by RAD52-mediated single-strand annealing. EMBO reports 62 11571269
2016 Identification of a Small Molecule Inhibitor of RAD52 by Structure-Based Selection. PloS one 57 26784987
2009 Rad52 recruitment is DNA replication independent and regulated by Cdc28 and the Mec1 kinase. The EMBO journal 56 19262568
2018 The concerted roles of FANCM and Rad52 in the protection of common fragile sites. Nature communications 55 30022024
2019 RAD52 Functions in Homologous Recombination and Its Importance on Genomic Integrity Maintenance and Cancer Therapy. Cancers 54 31652722
2018 Structural Basis of Homology-Directed DNA Repair Mediated by RAD52. iScience 53 30428330
2019 Emerging Roles of RAD52 in Genome Maintenance. Cancers 50 31340507
2004 Human and yeast Rad52 proteins promote DNA strand exchange. Proceedings of the National Academy of Sciences of the United States of America 50 15205482
2020 Strong suppression of gene conversion with increasing DNA double-strand break load delimited by 53BP1 and RAD52. Nucleic acids research 49 31832684
2017 Human RAD52 interactions with replication protein A and the RAD51 presynaptic complex. The Journal of biological chemistry 48 28551686
2008 Distinct RAD51 associations with RAD52 and BCCIP in response to DNA damage and replication stress. Cancer research 48 18413737
2009 Role of the Rad52 amino-terminal DNA binding activity in DNA strand capture in homologous recombination. The Journal of biological chemistry 47 19812039
2011 Inherited variation at chromosome 12p13.33, including RAD52, influences the risk of squamous cell lung carcinoma. Cancer discovery 46 22585858
2008 Functional and structural basis for a bacteriophage homolog of human RAD52. Current biology : CB 46 18656357
2005 Identification of residues important for DNA binding in the full-length human Rad52 protein. Journal of molecular biology 46 15571718
2021 RAD52: Paradigm of Synthetic Lethality and New Developments. Frontiers in genetics 44 34887904
2024 Mechanism of single-stranded DNA annealing by RAD52-RPA complex. Nature 43 38658755
2003 Yeast Rad52 and Rad51 recombination proteins define a second pathway of DNA damage assessment in response to a single double-strand break. Molecular and cellular biology 43 14612428
2019 Rad52 Restrains Resection at DNA Double-Strand Break Ends in Yeast. Molecular cell 42 31542296
2003 Rad52 and Ku bind to different DNA structures produced early in double-strand break repair. Nucleic acids research 42 12954758
2021 BRCA1 and RNAi factors promote repair mediated by small RNAs and PALB2-RAD52. Nature 41 33536619
2021 Nickel nanoparticle-induced cell transformation: involvement of DNA damage and DNA repair defect through HIF-1α/miR-210/Rad52 pathway. Journal of nanobiotechnology 41 34789290
2019 RAD52 as a Potential Target for Synthetic Lethality-Based Anticancer Therapies. Cancers 40 31615159
2009 The recombination protein RAD52 cooperates with the excision repair protein OGG1 for the repair of oxidative lesions in mammalian cells. Molecular and cellular biology 40 19506022
2000 The Saccharomyces cerevisiae DNA recombination and repair functions of the RAD52 epistasis group inhibit Ty1 transposition. Genetics 40 10655210
2012 A RAD52-like single-stranded DNA binding protein affects mitochondrial DNA repair by recombination. The Plant journal : for cell and molecular biology 39 22762281
2003 The Rad52-Rad59 complex interacts with Rad51 and replication protein A. DNA repair 39 13679150
2011 Mgm101 is a Rad52-related protein required for mitochondrial DNA recombination. The Journal of biological chemistry 38 22027892
2009 Human replication protein A-Rad52-single-stranded DNA complex: stoichiometry and evidence for strand transfer regulation by phosphorylation. Biochemistry 37 19530647
2008 Mechanisms of Rad52-independent spontaneous and UV-induced mitotic recombination in Saccharomyces cerevisiae. Genetics 37 18458103
2017 Yeast Srs2 Helicase Promotes Redistribution of Single-Stranded DNA-Bound RPA and Rad52 in Homologous Recombination Regulation. Cell reports 36 29045827
2009 Dynamic regulatory interactions of rad51, rad52, and replication protein-a in recombination intermediates. Journal of molecular biology 35 19445949
1991 Effects of controlled RAD52 expression on repair and recombination in Saccharomyces cerevisiae. Molecular and cellular biology 35 2005894
2023 Different SWI/SNF complexes coordinately promote R-loop- and RAD52-dependent transcription-coupled homologous recombination. Nucleic acids research 33 37470997
2008 Compensatory role for Rad52 during recombinational repair in Ustilago maydis. Molecular microbiology 33 18208529
1996 Self-association of human RAD52 protein. Mutation research 32 8879274
2014 Rad51-Rad52 mediated maintenance of centromeric chromatin in Candida albicans. PLoS genetics 31 24762765
2006 Multiple start codons and phosphorylation result in discrete Rad52 protein species. Nucleic acids research 30 16707661
2006 Rad52 and Rad59 exhibit both overlapping and distinct functions. DNA repair 30 16987715
2020 DSS1 interacts with and stimulates RAD52 to promote the repair of DSBs. Nucleic acids research 29 31799622
2018 Rad52-Rad51 association is essential to protect Rad51 filaments against Srs2, but facultative for filament formation. eLife 29 29985128
2006 Different mating-type-regulated genes affect the DNA repair defects of Saccharomyces RAD51, RAD52 and RAD55 mutants. Genetics 29 16782999
2004 Loss of Rad52 partially rescues tumorigenesis and T-cell maturation in Atm-deficient mice. Oncogene 29 15122331
2000 DNA damage-inducible and RAD52-independent repair of DNA double-strand breaks in Saccharomyces cerevisiae. Genetics 28 10757755
2022 SF3B4 promotes ovarian cancer progression by regulating alternative splicing of RAD52. Cell death & disease 26 35210412
2011 Rad52 function prevents chromosome loss and truncation in Candida albicans. Molecular microbiology 26 21272099
2010 Timing is everything: cell cycle control of Rad52. Cell division 24 20178629
2005 Virulence and karyotype analyses of rad52 mutants of Candida albicans: regeneration of a truncated chromosome of a reintegrant strain (rad52/RAD52) in the host. Infection and immunity 24 16299301
2020 Non-recombinogenic roles for Rad52 in translesion synthesis during DNA damage tolerance. EMBO reports 23 33289333
2009 Telomere maintenance and survival in saccharomyces cerevisiae in the absence of telomerase and RAD52. Genetics 23 19380905
2002 Differential expression and requirements for Schizosaccharomyces pombe RAD52 homologs in DNA repair and recombination. Nucleic acids research 22 11884628
2023 The cryo-EM structure of full-length RAD52 protein contains an undecameric ring. FEBS open bio 21 36707939
2023 Yeast Rad52 is a homodecamer and possesses BRCA2-like bipartite Rad51 binding modes. Nature communications 21 37798272
2002 Rad52 protein has a second stimulatory role in DNA strand exchange that complements replication protein-A function. The Journal of biological chemistry 21 12004070
2020 Physiological and Pathological Roles of RAD52 at DNA Replication Forks. Cancers 20 32050645

Missed literature

Know a paper Affinage missed for RAD52? Flag it for the maintainers and the community.

No submissions yet.