Affinage

RAD52

DNA repair protein RAD52 homolog · UniProt P43351

Length
418 aa
Mass
46.2 kDa
Annotated
2026-04-28
100 papers in source corpus 51 papers cited in narrative 51 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

RAD52 is a ring-forming ssDNA-binding protein central to homologous recombination and replication stress responses, functioning through DNA strand annealing, mediator-assisted RAD51 filament assembly, second-end capture, inverse strand exchange, and replication fork protection. Its conserved N-terminal domain binds ssDNA in a positively charged channel on the ring surface with bases exposed for Watson-Crick pairing, catalyzing annealing of RPA-coated complementary strands via open-ring complexes that interact with RPA through the RAD52 RPA-interacting domain and the RPA2 winged helix domain (PMID:38658755, PMID:30428330, PMID:8855248). RAD52 activity is regulated by c-Abl phosphorylation at Y104 (enhancing ssDNA annealing by reducing dsDNA binding) (PMID:21804533), CDK1 phosphorylation in G2/M (controlling ring–ring affinity for cell-cycle-specific HR activation) (PMID:32083180), and SUMOylation (inhibiting DNA binding as a pathway-choice quality control mechanism) (PMID:20371517). Beyond classical HR, RAD52 is essential for mitotic DNA synthesis at common fragile sites, break-induced replication at telomeres, replication fork protection against SMARCAL1-mediated reversal, and restraint of Sgs1/BLM-dependent end resection, and together with BRCA2 it suppresses POLθ-mediated end joining, explaining their synthetic lethal relationship in BRCA-deficient cancers (PMID:27984745, PMID:43658755, PMID:31542296, PMID:34616022).

Mechanistic history

Synthesis pass · year-by-year structured walk · 16 steps
  1. 1996 High

    The fundamental biochemical activity of Rad52 was established as a DNA-binding protein with potent strand annealing activity localized to its conserved N-terminus, answering how Rad52 contributes to recombination at the molecular level.

    Evidence Recombinant yeast Rad52 purification with in vitro DNA binding and annealing kinetics assays

    PMID:8855248

    Open questions at the time
    • Human RAD52 activity not yet characterized
    • Structural basis of ring formation unknown
    • Relationship to Rad51-mediated strand exchange unclear
  2. 1998 High

    Rad52 was shown to form multimeric rings, cooperate specifically with RPA (not other SSBs) for annealing enhancement, and physically interact with Rad51 to stimulate strand exchange, establishing it as a dual-function mediator bridging RPA-coated ssDNA and Rad51 filament assembly.

    Evidence Electron microscopy of ring structures, in vitro annealing with RPA specificity controls, and reconstituted Rad51 strand exchange stimulation assay

    PMID:9450759 PMID:9619627 PMID:9679065

    Open questions at the time
    • How the ring structure accommodates ssDNA unknown
    • Human RAD52 ring stoichiometry not determined
    • Mechanism of Rad51 loading unclear
  3. 1999 High

    Human RAD52 was found to bind DSB ends and protect them from exonuclease degradation, while c-Abl-dependent phosphorylation after IR was shown to regulate RAD52-RAD51 complex formation, linking RAD52 to DNA damage signaling.

    Evidence In vitro DSB binding and exonuclease protection assays; co-immunoprecipitation and kinase assays in ATM/c-Abl-deficient cells

    PMID:10212258 PMID:10227297

    Open questions at the time
    • Phosphorylation site not mapped
    • In vivo relevance of end protection unknown
  4. 2000 High

    Structural studies defined human RAD52 as a heptameric ring and revealed that ssDNA wraps on the ring exterior with a 4-nt periodicity, providing the structural framework for understanding annealing mechanism.

    Evidence EM/STEM 3D reconstruction of heptameric rings; hydroxyl radical footprinting of ssDNA on RAD52

    PMID:10744977 PMID:10921897

    Open questions at the time
    • High-resolution atomic structure lacking
    • How complementary strands find each other through ring complexes unknown
  5. 2001 High

    RAD52 was shown to possess a Rad51-independent homologous pairing activity residing in the N-terminal ring-forming domain, and to promote SSA by forming large complexes at annealed termini, establishing two separable recombination functions.

    Evidence In vitro homologous pairing assay with N-terminal truncation (1-237); EM visualization of SSA intermediates

    PMID:11454867 PMID:11459964 PMID:11571269

    Open questions at the time
    • Relative in vivo importance of RAD52-dependent pairing vs. RAD51 mediator function unclear
    • How pathway choice between SSA and gene conversion is controlled unknown
  6. 2002 High

    The c-Abl phosphorylation site on RAD52 was mapped to Y104, and its modification was shown to be required for IR-induced focus formation, identifying the first specific regulatory residue.

    Evidence In vitro kinase assay, Y104F mutagenesis, focus formation assay after IR

    PMID:12379650

    Open questions at the time
    • Biochemical consequence of Y104 phosphorylation on annealing activity not yet determined
  7. 2004 High

    ChIP kinetics at defined DSBs resolved three temporally distinct roles for Rad52 (presynaptic Rad51 assembly, synaptic co-occupancy, and postsynaptic functions), while in vitro assays demonstrated intrinsic D-loop formation and strand exchange activities, revealing RAD52 operates at multiple steps of HR.

    Evidence Time-course ChIP at HO-induced DSBs; in vitro D-loop and strand exchange assays with truncation mapping

    PMID:14765116 PMID:15205482 PMID:15205484

    Open questions at the time
    • How RAD52 transitions between these roles in vivo unknown
    • Structural basis of D-loop formation by RAD52 rings unclear
  8. 2008 High

    RAD52 was shown to catalyze second-end capture following Rad51-mediated strand invasion, specifically coupled to DNA polymerase eta-mediated D-loop extension, establishing RAD52's critical role in completing DSB repair by gene conversion.

    Evidence Reconstituted second-end capture assay with multiple DNA polymerases tested; a second dsDNA-binding site identified by structure-based mutagenesis essential for D-loop formation

    PMID:18313388 PMID:18593704 PMID:19074292

    Open questions at the time
    • Whether second-end capture is the essential in vivo function of RAD52 in mammals remains ambiguous
    • Structural basis of the second DNA binding site at atomic resolution unknown
  9. 2010 High

    SUMOylation of Rad52, enhanced by ssDNA, was found to inhibit DNA binding and annealing, shifting repair from SSA toward gene conversion, establishing post-translational modification as a pathway-choice mechanism.

    Evidence In vitro SUMO modification assay, DNA binding with SUMOylated protein, live-cell foci kinetics, recombination assays in SUMO-deficient mutants

    PMID:20371517

    Open questions at the time
    • SUMO modification sites not fully mapped
    • Whether SUMOylation regulates human RAD52 similarly unknown
  10. 2011 High

    Y104 phosphorylation by c-Abl was mechanistically resolved: it reduces dsDNA binding while enhancing ssDNA targeting, explaining how phosphorylation activates annealing by overcoming dsDNA inhibition.

    Evidence Amber suppressor incorporation of phosphotyrosine analogue at Y104, single-molecule FRET analysis

    PMID:21804533

    Open questions at the time
    • Whether Y104 phosphorylation similarly affects D-loop or inverse strand exchange activities unknown
  11. 2016 High

    RAD52 was identified as essential for replication stress responses: it is required for mitotic DNA synthesis (MiDAS) at common fragile sites (independent of RAD51/BRCA2) and for restart of collapsed replication forks, revealing major RAD51-independent functions in mammalian cells.

    Evidence siRNA/CRISPR knockout with mitotic EdU incorporation and fork restart assays; RAD52 distinguished from RAD51/BRCA2 requirements

    PMID:27984745 PMID:27984746

    Open questions at the time
    • How RAD52 recruits MUS81-EME1 mechanistically unknown
    • Whether MiDAS explains essentiality of RAD52 in BRCA-deficient cells unclear
  12. 2017 High

    A novel catalytic activity — inverse strand exchange with RNA templates — was discovered for RAD52, providing the biochemical basis for RNA-templated DSB repair and extending RAD52 function to non-dividing cells.

    Evidence In vitro inverse strand exchange assay with ssRNA; in vivo RNA-templated repair in yeast; RAD52 recruitment to DSBs in post-mitotic neurons dependent on nascent mRNA

    PMID:28602639 PMID:29217771

    Open questions at the time
    • Physiological importance of RNA-templated repair in mammalian tissues not established
    • Whether RAD52 directly binds RNA:DNA hybrids at endogenous loci requires genome-wide analysis
  13. 2019 High

    RAD52 was shown to protect stalled replication forks by counteracting SMARCAL1-mediated fork reversal and to restrain Sgs1/BLM-dependent DNA end resection by competing for DNA end binding, expanding its role as a regulator of DNA processing enzymes.

    Evidence In vitro fork remodeling and single-molecule translocation assays; genetic epistasis in two yeast species with resection rate measurements

    PMID:30926821 PMID:31542296

    Open questions at the time
    • Whether fork protection and resection restraint functions are coordinated or independent unclear
    • How RAD52 selects between protective and recombinogenic modes at forks unknown
  14. 2020 High

    CDK1 phosphorylation of Rad52 in G2/M was found to enhance ring–ring interactions, establishing a cell-cycle gating mechanism for HR activation, while Rad52 repair centers were shown to form liquid droplets that fuse via microtubule-dependent transport.

    Evidence In vitro kinase assay with CDK1-cyclin, mutagenesis of phosphosites with ring interaction assays; live-cell imaging of liquid droplet properties

    PMID:32019927 PMID:32083180

    Open questions at the time
    • Whether CDK1-regulated ring interactions are conserved in human RAD52 unknown
    • Functional significance of liquid droplet properties for repair efficiency not quantified
  15. 2021 High

    The synthetic lethal relationship between RAD52 and BRCA2 was biochemically explained: both proteins block POLθ-mediated end joining, and RAD52 loss causes premature TMEJ and chromosomal fusions in BRCA2-deficient cells.

    Evidence In vitro POLθ inhibition assay with purified RAD52 and BRCA2; TMEJ assays in double-deficient cells

    PMID:34616022

    Open questions at the time
    • Whether RAD52 directly binds POLθ or acts on the DNA substrate unclear
    • Therapeutic window of RAD52 inhibition in BRCA-deficient cancers not established from this study
  16. 2024 High

    Cryo-EM structures revealed that the active form of RAD52 is an open ring (not a closed undecamer), with ssDNA threading through a positively charged channel; annealing is driven by N-terminal domains while C-terminal regions modulate open-ring conformation and RPA2 winged helix interaction, providing the definitive structural mechanism.

    Evidence Cryo-EM atomic models of RAD52-RPA-ssDNA complexes with supporting biochemical annealing assays

    PMID:38658755

    Open questions at the time
    • Structures of RAD52 engaged in D-loop, inverse strand exchange, or fork protection not available
    • How open-ring dynamics are regulated by phosphorylation and SUMOylation at the structural level unknown

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include the structural basis of RAD52's fork protection and inverse strand exchange activities, how post-translational modifications (Y104 phosphorylation, CDK1 phosphorylation, SUMOylation) remodel the open-ring structure, and whether RAD52's multiple activities can be pharmacologically separated for therapeutic targeting in BRCA-deficient cancers.
  • No structure of RAD52 at replication forks or performing inverse strand exchange
  • Integrated structural model incorporating PTM effects on open-ring conformation lacking
  • In vivo separation-of-function for annealing vs. mediator vs. fork protection activities incomplete

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0003677 DNA binding 7 GO:0140096 catalytic activity, acting on a protein 3 GO:0003723 RNA binding 1
Localization
GO:0005634 nucleus 5 GO:0005694 chromosome 2
Pathway
R-HSA-73894 DNA Repair 8 R-HSA-69306 DNA Replication 3 R-HSA-1640170 Cell Cycle 2
Partners
DSS1OGG1PALB2POLD3RAD51RAD59RPAWRN

Evidence

Reading pass · 51 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1996 Yeast Rad52 is a DNA binding protein that binds both single- and double-stranded DNA and promotes DNA strand annealing at a rate 3500-fold faster than spontaneous annealing; a DNA binding domain was identified in the evolutionarily conserved N-terminus. Recombinant protein purification, in vitro DNA binding assays, DNA annealing kinetics assay Proceedings of the National Academy of Sciences of the United States of America High 8855248
1998 Yeast Rad52 forms multimeric ring structures, binds ssDNA and alters its conformation, and cooperates with RPA (but not E. coli SSB or T4 gp32) to enhance annealing of complementary ssDNA molecules; the Rad52-RPA interaction is essential for this enhancement. Electron microscopy, fluorescence assay with epsilon-DNA, protein-protein interaction studies, in vitro annealing assays Genes to cells : devoted to molecular & cellular mechanisms High 9619627
1998 Yeast Rad52 physically binds Rad51, and this interaction is necessary for Rad52 to stimulate Rad51-mediated strand exchange reactions and nucleoprotein filament formation. In vitro strand exchange assay, protein-protein binding assays with purified proteins Nature High 9450759
1998 Yeast Rad52 forms cytologically detectable subnuclear foci with RPA during meiosis; DSBs promote Rad52, RPA, and Rad51 focus formation; Rad52, Rad55, and Rad57 are required for assembly of Rad51 meiotic foci, supporting a role for Rad52 in promoting strand exchange complex assembly. Immunostaining, colocalization of Rad52 and RPA foci, mutant analysis Genes & development High 9679065
1999 Human RAD52 binds directly to DNA double-strand breaks, protects DNA ends from exonuclease attack, and facilitates end-to-end DNA interactions, suggesting a role in initiating homologous recombination. In vitro DSB binding assays, exonuclease protection assays, electron microscopy Nature High 10227297
1999 Radiation-induced Rad52 tyrosine phosphorylation by c-Abl (dependent on ATM) enhances complex formation between Rad51 and Rad52; ATM, c-Abl, and Rad51 can be co-immunoprecipitated; c-Abl phosphorylates Rad51 in vitro and in vivo. Co-immunoprecipitation, in vitro kinase assay, cell-based phosphorylation assay The Journal of biological chemistry High 10212258
2000 Human RAD52 forms heptameric rings with a large central channel, as determined by electron microscopy and STEM with 3D reconstruction. Transmission electron microscopy, scanning transmission electron microscopy, 3D reconstruction Current biology : CB High 10744977
2000 The C-terminal globular domain of RPA32 binds RAD52, UNG2, and XPA through a common structural surface; NMR structures defined the RPA32 domain and its complex with UNG2, establishing a structural basis for RPA's role in linking different DNA repair pathways. NMR structure determination, protein-protein interaction studies Cell High 11081631
2000 Human RAD52 binds ssDNA and tailed duplex DNA via precise interactions with the terminal base, creating a 4-nucleotide repeat hypersensitivity pattern phased from the terminus over ~36 nucleotides, suggesting ssDNA lies on an exposed surface of the protein ring. Hydroxyl radical footprinting, nuclease protection assays The EMBO journal High 10921897
2000 Mammalian Rad51 and GFP-Rad52 colocalize in distinct nuclear foci after DNA damage in murine cells; cells expressing GFP-Rad52 show increased survival and more Rad51 foci, providing in vivo evidence for their coordinated function in the DNA damage response. Live-cell fluorescence microscopy, survival assays, focus formation analysis EMBO reports Medium 11256631
2001 Yeast Rad52-GFP relocalizes from diffuse nuclear distribution to distinct foci after DSBs induced by gamma-irradiation, meiosis, or HO endonuclease, almost exclusively during S phase; replication mutants dramatically increase focus formation, linking recombinational repair to DNA replication. Live-cell fluorescence microscopy, GFP fusion protein, genetic analysis with replication and checkpoint mutants Proceedings of the National Academy of Sciences of the United States of America High 11459964
2001 Human Rad52 promotes homologous pairing via presynaptic complex formation with ssDNA; the N-terminal fragment (residues 1-237) that cannot bind Rad51 forms nucleoprotein filaments with ssDNA and promotes homologous pairing as efficiently as wild-type, revealing a Rad51-independent pairing activity. In vitro homologous pairing assay, electron microscopy of nucleoprotein filaments, domain truncation analysis The Journal of biological chemistry High 11454867
2001 Human RAD52 protein binds resected DSBs, promotes associations between complementary DNA termini, and forms large protein complexes at heteroduplex joints; electron microscopy visualized recombination intermediates with multiple RAD52 rings bound at annealed termini. In vitro SSA assay, electron microscopy of reaction intermediates EMBO reports High 11571269
2002 c-Abl tyrosine kinase phosphorylates Rad52 on tyrosine 104; this phosphorylation is induced by ionizing radiation and is required for proper IR-induced Rad52 nuclear foci formation; cells expressing phosphorylation-resistant Rad52 (Y104F) show compromised focus formation. In vitro kinase assay, mutagenesis (Y104F), nuclear focus formation assay after IR The Journal of biological chemistry High 12379650
2003 Time-lapse microscopy demonstrates that Rad52 foci colocalize with DSBs, that Rad52 focus formation is rapid and reversible, and that a single Rad52 repair center can simultaneously recruit more than one DSB. Time-lapse fluorescence microscopy, fluorescently marked DSB system in yeast Nature cell biology High 12766777
2003 WRN and RAD52 form a complex in vivo that co-localizes at arrested replication forks; RAD52 both inhibits and enhances WRN helicase activity in a DNA-structure-dependent manner; WRN increases efficiency of RAD52-mediated strand annealing. FRET analysis, co-localization at replication forks, in vitro helicase and annealing assays The Journal of biological chemistry High 12750383
2003 Ku and human Rad52 bind to different DNA substrates: Ku binds preferentially to DNA ends, while Rad52 binds preferentially to ssDNA and aggregates different ssDNA molecules; they do not compete for the same broken DNA ends, suggesting they act at different stages of DSB repair. In vitro DNA binding assays with defined substrates Nucleic acids research High 12954758
2003 Rad52 forms complexes with Rad51, RPA, or Rad59; the N-terminal self-interaction region of Rad52 is required for interaction with Rad59; Rad59 also self-interacts suggesting homomeric and heteromeric ring formation. Co-immunoprecipitation from yeast extracts, deletion analysis DNA repair Medium 13679150
2004 In vivo ChIP kinetics at HO-induced DSBs revealed three distinct roles for Rad52: (1) presynaptic role required for Rad51 assembly, (2) synaptic role with Rad51 filaments, and (3) postsynaptic role after Rad51 dissociates; a ssDNA complex containing both Rad51 and Rad52 was detected biochemically. Immunofluorescence and chromatin immunoprecipitation with time-course analysis, in vitro biochemical studies The EMBO journal High 14765116
2004 Human and yeast Rad52 promote DNA strand exchange; the N-terminal domain of HsRad52 (residues 1-237) containing the ring-forming residues is sufficient for strand exchange, while other truncated domains are inactive; yield is proportional to A-T content. In vitro strand exchange assay with purified proteins and truncation mutants Proceedings of the National Academy of Sciences of the United States of America High 15205482
2004 Human Rad52 protein catalyzes D-loop formation and strand exchange; stoichiometric complex formation between RAD52 and ssDNA is critical for strand exchange, while coating of both ssDNA and dsDNA inhibits the reaction. In vitro D-loop and strand exchange assays, DNase I protection assay Proceedings of the National Academy of Sciences of the United States of America High 15205484
2004 RAD52 suppresses retroviral integration by competing with active integration complexes for the retroviral cDNA genome; RAD52-deficient mammalian cells show markedly increased retroviral integration, and this function is distinct from the HR pathway per se. Retroviral transduction assay in RAD52-deficient cells, comparison with XRCC2/3 and BRCA2 mutants The EMBO journal Medium 15297876
2005 Alanine-scanning mutagenesis of the N-terminal domain of full-length HsRad52 identified specific residues responsible for direct contact with ssDNA; the 7-subunit ring of full-length protein has DNA-binding and cross-subunit interactions that differ from the 11-subunit ring of truncation mutants in crystal structures. Saturating alanine-scanning mutagenesis, DNA binding assays Journal of molecular biology High 15571718
2006 Rad51 protein prevents Rad52-mediated annealing of complementary ssDNA in an ATP-dependent manner through direct interaction; the Rad51 nucleoprotein filament is more effective at inhibiting annealing than free Rad51; Rad59 partially restores Rad52-dependent annealing in the presence of Rad51, suggesting coordination in pathway choice. In vitro ssDNA annealing assay with purified proteins, protein-protein interaction studies The Journal of biological chemistry High 18337252
2006 Rad52 anneals RPA-coated ssDNA while Rad59 cannot; Rad59-promoted annealing follows first-order kinetics whereas Rad52 follows second-order kinetics; Rad59 enhances Rad52-mediated annealing in high salt conditions, indicating they perform different functions. Quantitative in vitro ssDNA annealing assays with purified Rad52 and Rad59 The Journal of biological chemistry High 16565518
2006 Rad52 is phosphorylated in both a cell-cycle-independent and cell-cycle-dependent manner; multiple Rad52 species arise from promiscuous start codon usage and phosphorylation; the Rad52 C-terminus is required for phosphorylation but interaction with Rad51 is not. Protein blot analysis, start codon mutagenesis, phosphatase treatment Nucleic acids research Medium 16707661
2008 Human RAD52 promotes annealing of the second ssDNA end following Rad51-mediated strand exchange; DNA repair synthesis by DNA polymerase eta (but not pol-delta or pol-iota) on a D-loop primer enables RAD52-dependent second-end capture; RPA stimulates but E. coli SSB does not. In vitro reconstituted second-end capture assay with purified proteins Molecular cell High 18313388
2008 A second DNA binding site was identified in human Rad52 by structure-based alanine scan mutagenesis; this site is essential for forming a ternary complex of Rad52-ssDNA-dsDNA and for catalyzing D-loop formation; Rad52 introduces positive supercoils into dsDNA using this second binding site. Structure-based alanine scanning mutagenesis, D-loop formation assay, DNA supercoiling assay The Journal of biological chemistry High 18593704
2008 Single-molecule FRET analysis revealed that human Rad52-mediated DNA annealing proceeds through successive steps involving rearrangements of ssDNA-Rad52 complexes; initial pairing is followed by search for extended homology without dissociation, driven by interaction between two overlapping nucleoprotein complexes. Single-molecule FRET, real-time imaging of annealing events Proceedings of the National Academy of Sciences of the United States of America High 19074292
2009 Rad52 mediates second ssDNA capture by annealing the strand displaced during Rad51-mediated strand exchange; RPA-t11 (recombination-deficient mutant) fails to interact with Rad52 and blocks this annealing, explaining its in vivo phenotype; E. coli RecO/SSB perform analogous reactions, showing conservation. In vitro strand capture assay with purified proteins, mutant RPA analysis The EMBO journal High 17093500
2009 The rad52-R70A mutation in the amino-terminal DNA binding domain abolishes DNA annealing but preserves Rad51 delivery to DNA; ChIP shows rad52-R70A associates with DSBs and recruits Rad51 normally but cannot complete recombination; cells can perform strand invasion but fail to capture the second end, requiring the conserved N-terminal DNA binding activity. Mutagenesis, in vitro biochemical assays, chromatin immunoprecipitation, recombination intermediate analysis The Journal of biological chemistry High 19812039
2009 RAD52 interacts with OGG1 in vitro and in vivo; RAD52 stimulates OGG1 incision activity; OGG1 inhibits RAD52 catalytic activities; RAD52 colocalizes with OGG1 after oxidative stress (but not after IR-induced DSBs); RAD52 depletion leads to increased oxidized base accumulation and sensitivity to oxidative stress. Co-immunoprecipitation, in vitro OGG1 incision assay, colocalization by microscopy, siRNA knockdown, base oxidation assays Molecular and cellular biology High 19506022
2010 Rad52 is SUMOylated in yeast; SUMOylation is enhanced by ssDNA; SUMO modification of Rad52 inhibits its DNA binding and annealing activities in vitro; SUMO-deficient Rad52 mutants show shorter spontaneous Rad52 foci duration in vivo and a shift from SSA to gene conversion, revealing SUMOylation as a quality control mechanism. In vitro SUMO modification assay, DNA binding assays with SUMOylated Rad52, live-cell fluorescence microscopy, recombination assays Nucleic acids research High 20371517
2011 c-Abl phosphorylation of RAD52 at tyrosine 104 enhances ssDNA annealing activity by reducing dsDNA binding affinity; RAD52(Y104pCMF) specifically targets and wraps ssDNA while unmodified RAD52 diffuses into dsDNA regions; phosphorylation allows overcoming dsDNA inhibition of annealing. Amber suppressor technology (phosphotyrosine analogue substitution), single-molecule FRET, DNA binding assays The EMBO journal High 21804533
2015 Rad55 bridges interaction between the Shu complex (Csm2/Psy3) and Rad51/Rad52; in a fully reconstituted system, the Shu complex synergizes with Rad55-Rad57 and Rad52 to promote Rad51 nucleation on RPA-coated ssDNA; the csm2-F46A allele disrupts Rad55 interaction and impairs Rad51 filament assembly in vitro and HR in vivo. Fully reconstituted in vitro Rad51 filament assembly assay, mutagenesis, HR assay in vivo Nature communications High 26215801
2016 Human RAD52 is required for mitotic DNA synthesis (MiDAS) at common fragile site loci; RAD52 (but not RAD51 or BRCA2) is needed for timely recruitment of MUS81-EME1 endonuclease and POLD3 to CFSs in early mitosis; loss of RAD52 impairs MiDAS. siRNA knockdown, CRISPR/Cas9 knockout, mitotic EdU incorporation assay, immunofluorescence focus analysis Molecular cell High 27984745
2016 Mammalian RAD52 localizes to DNA replication stress foci; RAD52 depletion or CRISPR knockout impairs restart of collapsed replication forks and leads to DNA damage in cells with oncogene-induced or chemically-induced fork collapse. siRNA knockdown, CRISPR/Cas9 knockout, replication fork restart assay, DNA damage foci analysis Molecular cell High 27984746
2017 Yeast and human Rad52 catalyze inverse strand exchange, in which Rad52 forms a complex with dsDNA and promotes strand exchange with homologous ssRNA or ssDNA; this activity is absent from Rad51 and Rad59; inverse strand exchange is important for RNA-templated DSB repair in vivo. In vitro inverse strand exchange assay with purified proteins, in vivo RNA-templated repair assay in yeast Molecular cell High 28602639
2017 RAD52 is recruited to sites of DNA DSBs in post-mitotic neurons dependent on nascent mRNA from active transcription, supporting an RNA-templated HR repair mechanism in non-dividing cells. Focus formation assay in neurons, transcription inhibition, siRNA knockdown The Journal of biological chemistry Medium 29217771
2017 Human RAD52 binds tightly to RPA-ssDNA complexes and imparts an inhibitory effect on RPA turnover; during presynaptic complex assembly, most RPA and RAD52 are displaced by RAD51 but some RAD52-RPA-ssDNA clusters persist; once RAD51 dissociates, new RAD52-binding events can occur. Single-molecule imaging, ssDNA curtains assay The Journal of biological chemistry High 28551686
2017 Srs2 helicase removes Rad52 from RPA-ssDNA complexes as it translocates along ssDNA, promoting redistribution of both Rad52 and RPA; Srs2 translocates at ~170 nt/s and is highly processive on RPA-coated ssDNA. Single-molecule imaging of Srs2 activity on defined ssDNA substrates with fluorescent Rad52 and RPA Cell reports High 29045827
2018 Crystal structures of human RAD52-ssDNA complexes revealed two conformations: a 'wrapped' conformation where ssDNA is in B-form around the ring with bases exposed for Watson-Crick pairing, and a 'trapped' conformation between two RAD52 rings using a second DNA binding site; these structures define key reaction intermediates of RAD52-mediated annealing. X-ray crystallography of RAD52-ssDNA complexes iScience High 30428330
2018 Purified RAD52 and BRCA2 proteins both block the DNA polymerase function of POLθ, providing a biochemical mechanism for their synthetic lethal relationships; RAD52 loss causes premature TMEJ usage in BRCA2-deficient cells and chromosomal fusions. In vitro POLθ inhibition assay with purified proteins, TMEJ assays in RAD52/BRCA2-deficient cells Nature cell biology High 34616022
2019 RAD52 binds to stalled replication forks, promotes their occlusion, and counteracts loading of SMARCAL1 in vitro and in vivo, thereby preventing excessive fork reversal and MRE11-mediated degradation of reversed forks. siRNA knockdown, small-molecule RAD52 inhibitor, in vitro fork remodeling assay, single-molecule analysis Nature communications High 30926821
2019 Yeast Rad52 inhibits Sgs1 (BLM homolog)-dependent DNA end resection; single-molecule analysis shows Rad52 competes with Sgs1 for DNA end binding and inhibits Sgs1 translocation; in rad52 mutants, Rqh1 (fission yeast Sgs1/BLM homolog)-dependent resection increases from 3-5 kb/h to 10-20 kb/h. Genetic analysis in S. pombe and S. cerevisiae, in vitro single-molecule analysis, resection rate measurement Molecular cell High 31542296
2019 DSS1 binds RAD52, changes its oligomeric conformation, modulates DNA binding properties, stimulates SSA activity, and promotes strand invasion; DSS1 is thus a functional partner of RAD52 in SSA and BIR pathways. Co-immunoprecipitation, in vitro SSA and strand invasion assays, oligomeric conformation analysis Nucleic acids research High 31799622
2020 In yeast, Rad52 DNA repair proteins at different damage sites assemble into liquid droplets that fuse via nuclear microtubule filaments; these droplets concentrate tubulin and project aster-like filaments to tether the repair center to longer filaments for nuclear periphery mobilization. Live-cell fluorescence microscopy, liquid droplet characterization, genetic analysis Nature communications Medium 32019927
2020 CDK1 (Cdc28) phosphorylates yeast Rad52 in G2/M phase with G2/M cyclins; non-phosphorylatable Rad52 mutations impair affinity between Rad52 rings, reducing their interaction; this phosphoregulation controls cell cycle-specific activation of homologous recombination. In vitro kinase assay, mutagenesis, DNA binding assays, cell cycle analysis Science advances High 32083180
2020 ROS-induced telomeric DNA damage triggers R-loop accumulation in a TERRA- and TRF2-dependent manner; RAD52 is recruited to telomeric R-loops through interactions with both CSB and DNA:RNA hybrids; RAD52 recruits POLD3 to enable BIR-mediated repair of telomeric DSBs. Chromatin immunoprecipitation, focus formation assay, co-immunoprecipitation, knockdown studies Nucleic acids research High 31777915
2021 BRCA1-RNAi protein complex generates single-stranded DNA-damage-associated small RNAs (sdRNAs) that promote DNA repair driven by the PALB2-RAD52 complex at transcriptional termination pause sites; this mechanism operates in both quiescent (G0) and proliferating cells. Identification of sdRNAs, co-immunoprecipitation of PALB2-RAD52 complex, repair assays Nature Medium 33536619
2024 Cryo-EM structures revealed that RAD52 forms open rings (not closed undecamers) as the active form; ssDNA annealing is driven by open RAD52 rings in association with RPA; ssDNA sits in a positively charged channel; N-terminal domains drive annealing while C-terminal regions modulate open-ring conformation and RPA interaction; critical interactions occur between the RPA-interacting domain of RAD52 and the winged helix domain of RPA2. Cryo-electron microscopy, atomic model building, biochemical annealing assays Nature High 38658755

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 823 12456786
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 391 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
2003 Colocalization of multiple DNA double-strand breaks at a single Rad52 repair centre. Nature cell biology 343 12766777
2016 RAD52 Facilitates Mitotic DNA Synthesis Following Replication Stress. Molecular cell 314 27984745
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
1980 The RAD52 gene is required for homothallic interconversion of mating types and spontaneous mitotic recombination in yeast. Proceedings of the National Academy of Sciences of the United States of America 234 6987653
1998 Rad52 associates with RPA and functions with rad55 and rad57 to assemble meiotic recombination complexes. Genes & development 228 9679065
1999 Radiation-induced assembly of Rad51 and Rad52 recombination complex requires ATM and c-Abl. The Journal of biological chemistry 219 10212258
2000 Structural basis for the recognition of DNA repair proteins UNG2, XPA, and RAD52 by replication factor RPA. Cell 214 11081631
2016 Mammalian RAD52 Functions in Break-Induced Replication Repair of Collapsed DNA Replication Forks. Molecular cell 211 27984746
1980 Effects of the RAD52 Gene on Recombination in SACCHAROMYCES CEREVISIAE. Genetics 196 17248995
1996 UBL1, a human ubiquitin-like protein associating with human RAD51/RAD52 proteins. Genomics 180 8812453
2000 The human Rad52 protein exists as a heptameric ring. Current biology : CB 174 10744977
2007 Genome-wide analysis of Rad52 foci reveals diverse mechanisms impacting recombination. PLoS genetics 168 18085829
2002 Classification and evolutionary history of the single-strand annealing proteins, RecT, Redbeta, ERF and RAD52. BMC genomics 166 11914131
1997 A newly identified DNA ligase of Saccharomyces cerevisiae involved in RAD52-independent repair of DNA double-strand breaks. Genes & development 160 9271115
2020 DNA repair by Rad52 liquid droplets. Nature communications 136 32019927
2001 Homologous pairing promoted by the human Rad52 protein. The Journal of biological chemistry 135 11454867
1996 Associations of UBE2I with RAD52, UBL1, p53, and RAD51 proteins in a yeast two-hybrid system. Genomics 127 8921390
1995 A novel allele of Saccharomyces cerevisiae RFA1 that is deficient in recombination and repair and suppressible by RAD52. Molecular and cellular biology 126 7862153
2017 Rad52 Inverse Strand Exchange Drives RNA-Templated DNA Double-Strand Break Repair. Molecular cell 111 28602639
2001 The yeast recombinational repair protein Rad59 interacts with Rad52 and stimulates single-strand annealing. Genetics 111 11606529
2003 WRN interacts physically and functionally with the recombination mediator protein RAD52. The Journal of biological chemistry 104 12750383
2008 DNA repair synthesis facilitates RAD52-mediated second-end capture during DSB repair. Molecular cell 102 18313388
2004 In vivo assembly and disassembly of Rad51 and Rad52 complexes during double-strand break repair. The EMBO journal 102 14765116
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
2021 POLθ-mediated end joining is restricted by RAD52 and BRCA2 until the onset of mitosis. Nature cell biology 88 34616022
1997 Human Rad52 protein promotes single-strand DNA annealing followed by branch migration. Mutation research 87 9219578
2017 RAD52 is required for RNA-templated recombination repair in post-mitotic neurons. The Journal of biological chemistry 84 29217771
2008 Human Rad52-mediated homology search and annealing occurs by continuous interactions between overlapping nucleoprotein complexes. Proceedings of the National Academy of Sciences of the United States of America 83 19074292
2016 Targeting BRCA1- and BRCA2-deficient cells with RAD52 small molecule inhibitors. Nucleic acids research 82 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 77 29334356
2019 Rad52 prevents excessive replication fork reversal and protects from nascent strand degradation. Nature communications 75 30926821
2000 Coordinated response of mammalian Rad51 and Rad52 to DNA damage. EMBO reports 75 11256631
2018 Simultaneous Targeting of PARP1 and RAD52 Triggers Dual Synthetic Lethality in BRCA-Deficient Tumor Cells. Cell reports 73 29898385
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 Rad51 protein controls Rad52-mediated DNA annealing. The Journal of biological chemistry 69 18337252
2008 Identification of a second DNA binding site in the human Rad52 protein. The Journal of biological chemistry 69 18593704
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
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
1999 Human Rad51 amino acid residues required for Rad52 binding. Journal of molecular biology 61 10448035
2011 Identification of plant RAD52 homologs and characterization of the Arabidopsis thaliana RAD52-like genes. The Plant cell 60 22202891
2015 Promotion of presynaptic filament assembly by the ensemble of S. cerevisiae Rad51 paralogues with Rad52. Nature communications 59 26215801
1998 Requirement for end-joining and checkpoint functions, but not RAD52-mediated recombination, after EcoRI endonuclease cleavage of Saccharomyces cerevisiae DNA. Molecular and cellular biology 59 9528760
2016 Identification of a Small Molecule Inhibitor of RAD52 by Structure-Based Selection. PloS one 57 26784987
2011 Tyrosine phosphorylation enhances RAD52-mediated annealing by modulating its DNA binding. The EMBO journal 56 21804533
2009 Conformational adaptability of Redbeta during DNA annealing and implications for its structural relationship with Rad52. Journal of molecular biology 56 19527729
2018 The concerted roles of FANCM and Rad52 in the protection of common fragile sites. Nature communications 55 30022024
1987 Purification and characterization of an endo-exonuclease from Saccharomyces cerevisiae that is influenced by the RAD52 gene. The Journal of biological chemistry 53 2826428
2019 RAD52 Functions in Homologous Recombination and Its Importance on Genomic Integrity Maintenance and Cancer Therapy. Cancers 52 31652722
2018 Structural Basis of Homology-Directed DNA Repair Mediated by RAD52. iScience 52 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
2017 Human RAD52 interactions with replication protein A and the RAD51 presynaptic complex. The Journal of biological chemistry 48 28551686
2011 Inherited variation at chromosome 12p13.33, including RAD52, influences the risk of squamous cell lung carcinoma. Cancer discovery 46 22585858
2009 Role of the Rad52 amino-terminal DNA binding activity in DNA strand capture in homologous recombination. The Journal of biological chemistry 46 19812039
2005 Identification of residues important for DNA binding in the full-length human Rad52 protein. Journal of molecular biology 46 15571718
2008 Functional and structural basis for a bacteriophage homolog of human RAD52. Current biology : CB 45 18656357
2021 RAD52: Paradigm of Synthetic Lethality and New Developments. Frontiers in genetics 44 34887904
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 40 33536619
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
2003 The Rad52-Rad59 complex interacts with Rad51 and replication protein A. DNA repair 39 13679150
2002 Regulation of ionizing radiation-induced Rad52 nuclear foci formation by c-Abl-mediated phosphorylation. The Journal of biological chemistry 39 12379650
2005 Potentiation of gene targeting in human cells by expression of Saccharomyces cerevisiae Rad52. Nucleic acids research 38 16106043
2024 Mechanism of single-stranded DNA annealing by RAD52-RPA complex. Nature 37 38658755
2011 Mgm101 is a Rad52-related protein required for mitochondrial DNA recombination. The Journal of biological chemistry 37 22027892
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
2000 Rad22 protein, a rad52 homologue in Schizosaccharomyces pombe, binds to DNA double-strand breaks. The Journal of biological chemistry 33 10956666
1996 Self-association of human RAD52 protein. Mutation research 32 8879274
2023 Different SWI/SNF complexes coordinately promote R-loop- and RAD52-dependent transcription-coupled homologous recombination. Nucleic acids research 31 37470997
2015 Functional characterization of RAD52 as a lung cancer susceptibility gene in the 12p13.33 locus. Molecular carcinogenesis 31 26013599
2008 Compensatory role for Rad52 during recombinational repair in Ustilago maydis. Molecular microbiology 31 18208529
2020 Phosphoregulation of Rad51/Rad52 by CDK1 functions as a molecular switch for cell cycle-specific activation of homologous recombination. Science advances 30 32083180
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
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
1999 Common nonsense mutations in RAD52. Cancer research 28 10463575
2015 Members of the RAD52 Epistasis Group Contribute to Mitochondrial Homologous Recombination and Double-Strand Break Repair in Saccharomyces cerevisiae. PLoS genetics 27 26540255
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
2004 Strand exchange activity of human recombination protein Rad52. Proceedings of the National Academy of Sciences of the United States of America 25 15205484