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RAD52 (RAD52 homolog (S. cerevisiae))

Written2014-02Benjamin H Lok, Simon N Powell
Memorial Sloan-Kettering Cancer Center, New York, New York 10065, USA

(Note : for Links provided by Atlas : click)


HGNC (Hugo) RAD52
HGNC Previous nameRAD52 (S. cerevisiae) homolog
 RAD52 homolog (S. cerevisiae)
LocusID (NCBI) 5893
Atlas_Id 349
Location 12p13.33  [Link to chromosome band 12p13]
Location_base_pair Starts at 911736 and ends at 949694 bp from pter ( according to GRCh38/hg38-Dec_2013)  [Mapping RAD52.png]
Fusion genes
(updated 2017)
Data from Atlas, Mitelman, Cosmic Fusion, Fusion Cancer, TCGA fusion databases with official HUGO symbols (see references in chromosomal bands)
SRCAP (16p11.2) / RAD52 (12p13.33)WNK1 (12p13.33) / RAD52 (12p13.33)


Note The human and murine RAD52 gene is composed of 12 exons. Kito et al. identified three RAD52 isoforms designated RAD52β (226 amino acids), RAD52γ (139 amino acids), and RAD52δ (118 amino acids) which were able to bind ssDNA and dsDNA much like reference RAD52 (RAD52α). However, these isoforms lacked the ability to associate with RAD52α (Kito et al., 1999).
Thorpe and colleagues describe two splice variants that conferred increased homology-directed repair in the murine RAD52 gene RAD52Δexon4 and RAD52+intron8 (Thorpe et al., 2006).


Note The human RAD52 (hRAD52) protein is similar to the Saccharomyces cerevisiae RAD52 protein (ScRAD52) both structurally and biochemically. However the phenotypic properties of RAD52, particularly in mediating homologous recombination varies amongst the evolutionary spectrum.
  Secondary structure of the hRAD52 protein. From (Creative Commons License).
Description hRAD52 protein is comprised of 418 amino acids and forms a heptameric ring (Stasiak et al., 2000), which is mediated by the N-terminus (Ranatunga et al., 2001). This N-terminal portion binds ssDNA (Mortensen et al., 1996).
The well-studied hRAD521-212 is the N-terminal portion which forms an undecameric ringed polymer (Kagawa et al., 2002). DNA binding properties are linked to various amino acids, including, Arg-55, Tyr-65, Lys-152, Arg-153, Arg-156. Arg-55 and Lys-152 are necessarily for ssDNA binding, whereas Tyr-65, Arg-152, and Arg-156 are essential for binding both ssDNA and dsDNA (Kagawa et al., 2002). Phe-79 and Lys-102 have also shown a role in ssDNA and dsDNA binding, respectively (Lloyd et al., 2005). Interfering with the Phe-79 of hRAD52 was recently demonstrated to disrupt the RAD52-DNA interaction leading to an accumulation of DNA double-strand breaks (DSBs) particularly in BRCA1/2 deficient cells (Cramer-Morales et al., 2013). Further study is required to decipher the hierarchy of these respective sites and study additional novel binding sites.
Please see the following diagram for the location of several of these amino acid sites.
  Secondary structure of the hRAD52 protein. From Kagawa et al. 2002, with permission from Elsevier.
  The hRAD521-212 undecameric polymer with principal DNA binding amino acid residues labeled residing in the predominantly positively charged groove. From Kagawa et al. 2002, with permission from Elsevier.
Localisation ScRAD52 is a nuclear protein and predominantly recruited into sub-nuclear foci during the S-phase of the cell cycle (Lisby et al., 2001). hRAD52 sub-nuclear foci formation after exposure to ionizing radiation is dependent on c-Abl-mediated phosphorylation (Kitao and Yuan, 2002).
Function ScRAD52 mediates RAD51 recombination activity and thus homology-directed repair (Milne and Weaver, 1993). hRAD52 also demonstrates this ability to stimulate homologous pairing by hRAD51 (Benson et al., 1998). The interaction of ScRAD52 and hRAD52 with replication protein A (RPA) is important for the binding with ssDNA by RAD52 (Hays et al., 1998; Shinohara et al., 1998; Jackson et al., 2002). hRAD52 binds directly to DSBs, protects them from exonuclease resection, and facilitates end-to-end interaction (Van Dyck et al., 1999). Furthermore, capture of the second DNA end in homologous recombination appears to involve RAD52-mediated annealing of RPA-ssDNA strands in biochemical reactions (Sugiyama et al., 2006).
Although, ScRAD52 and hRAD52 does not stimulate RAD51 DNA strand exchange with RPA-ssDNA complexes in biochemical assays (Jensen et al., 2010), under certain conditions, hRAD52 does promote RAD51-mediated homologous DNA pairing (Baumann and West, 1999).
hRAD52 mediates RAD51 recombination function in human cancer cells deficient in BRCA1 (Cramer-Morales et al., 2013; Lok et al., 2013), PALB2 (Lok et al., 2013) or BRCA2 (Feng et al., 2011). RAD52 is able to mediate RAD51-mediated homology-directed repair when the predominant BRCA1-PALB2-BRCA2 homologous recombination pathway is perturbed (see figure below). The RAD52-RAD51 pathway also appears to function independently of the RAD51 paralogs RAD51B/RAD51C/RAD51D-XRCC2 (Chun et al., 2013).
ScRAD52 is required for RAD51-independent single-strand annealing (SSA) (Singleton et al., 2002; Symington, 2002) and break-induced replication (BIR) (Malkova et al., 1996; Ira and Haber, 2002; McEachern and Haber, 2006).
  The BRCA and RAD52 pathways of DNA double-strand break repair. *There is currently no well-defined evidence that single-end DSBs or daughter-strand gaps are repaired by single strand annealing. From Lok and Powell, 2012.


Note Currently, there are no known mutations of RAD52 that lead to human disease, including none associated with breast cancer (Bell et al., 1999), ovarian cancer (Tong et al., 2003; Beesley et al., 2007) or chronic lymphocytic leukemia (Sellick et al., 2008).

Implicated in

Entity Resistance to platinum-based chemotherapy
Prognosis There is a report of uncertain significance by Shi et al. that may link certain RAD52 variants and RAD52 protein expression levels to resistance to platinum-based chemotherapy (Shi et al., 2012), however no other published studies have demonstrated a similar association.


Heteroduplex formation by human Rad51 protein: effects of DNA end-structure, hRP-A and hRad52.
Baumann P, West SC.
J Mol Biol. 1999 Aug 13;291(2):363-74.
PMID 10438626
Association between single-nucleotide polymorphisms in hormone metabolism and DNA repair genes and epithelial ovarian cancer: results from two Australian studies and an additional validation set.
Beesley J, Jordan SJ, Spurdle AB, Song H, Ramus SJ, Kjaer SK, Hogdall E, DiCioccio RA, McGuire V, Whittemore AS, Gayther SA, Pharoah PD, Webb PM, Chenevix-Trench G; Australian Ovarian Cancer Study Group; Australian Cancer Study (Ovarian Cancer); Australian Breast Cancer Family Study.
Cancer Epidemiol Biomarkers Prev. 2007 Dec;16(12):2557-65.
PMID 18086758
Common nonsense mutations in RAD52.
Bell DW, Wahrer DC, Kang DH, MacMahon MS, FitzGerald MG, Ishioka C, Isselbacher KJ, Krainer M, Haber DA.
Cancer Res. 1999 Aug 15;59(16):3883-8.
PMID 10463575
Synergistic actions of Rad51 and Rad52 in recombination and DNA repair.
Benson FE, Baumann P, West SC.
Nature. 1998 Jan 22;391(6665):401-4.
PMID 9450758
Rad51 paralog complexes BCDX2 and CX3 act at different stages in the BRCA1-BRCA2-dependent homologous recombination pathway.
Chun J, Buechelmaier ES, Powell SN.
Mol Cell Biol. 2013 Jan;33(2):387-95. doi: 10.1128/MCB.00465-12. Epub 2012 Nov 12.
PMID 23149936
Personalized synthetic lethality induced by targeting RAD52 in leukemias identified by gene mutation and expression profile.
Cramer-Morales K, Nieborowska-Skorska M, Scheibner K, Padget M, Irvine DA, Sliwinski T, Haas K, Lee J, Geng H, Roy D, Slupianek A, Rassool FV, Wasik MA, Childers W, Copland M, Muschen M, Civin CI, Skorski T.
Blood. 2013 Aug 15;122(7):1293-304. doi: 10.1182/blood-2013-05-501072. Epub 2013 Jul 8.
PMID 23836560
Rad52 inactivation is synthetically lethal with BRCA2 deficiency.
Feng Z, Scott SP, Bussen W, Sharma GG, Guo G, Pandita TK, Powell SN.
Proc Natl Acad Sci U S A. 2011 Jan 11;108(2):686-91. doi: 10.1073/pnas.1010959107. Epub 2010 Dec 8.
PMID 21148102
Studies of the interaction between Rad52 protein and the yeast single-stranded DNA binding protein RPA.
Hays SL, Firmenich AA, Massey P, Banerjee R, Berg P.
Mol Cell Biol. 1998 Jul;18(7):4400-6.
PMID 9632824
Characterization of RAD51-independent break-induced replication that acts preferentially with short homologous sequences.
Ira G, Haber JE.
Mol Cell Biol. 2002 Sep;22(18):6384-92.
PMID 12192038
Analysis of the human replication protein A:Rad52 complex: evidence for crosstalk between RPA32, RPA70, Rad52 and DNA.
Jackson D, Dhar K, Wahl JK, Wold MS, Borgstahl GE.
J Mol Biol. 2002 Aug 2;321(1):133-48.
PMID 12139939
Purified human BRCA2 stimulates RAD51-mediated recombination.
Jensen RB, Carreira A, Kowalczykowski SC.
Nature. 2010 Oct 7;467(7316):678-83. doi: 10.1038/nature09399.
PMID 20729832
Crystal structure of the homologous-pairing domain from the human Rad52 recombinase in the undecameric form.
Kagawa W, Kurumizaka H, Ishitani R, Fukai S, Nureki O, Shibata T, Yokoyama S.
Mol Cell. 2002 Aug;10(2):359-71.
PMID 12191481
Regulation of ionizing radiation-induced Rad52 nuclear foci formation by c-Abl-mediated phosphorylation.
Kitao H, Yuan ZM.
J Biol Chem. 2002 Dec 13;277(50):48944-8. Epub 2002 Oct 11.
PMID 12379650
Identification of novel isoforms of human RAD52.
Kito K, Wada H, Yeh ET, Kamitani T.
Biochim Biophys Acta. 1999 Dec 23;1489(2-3):303-14.
PMID 10673031
Rad52 forms DNA repair and recombination centers during S phase.
Lisby M, Rothstein R, Mortensen UH.
Proc Natl Acad Sci U S A. 2001 Jul 17;98(15):8276-82.
PMID 11459964
Identification of residues important for DNA binding in the full-length human Rad52 protein.
Lloyd JA, McGrew DA, Knight KL.
J Mol Biol. 2005 Jan 14;345(2):239-49.
PMID 15571718
RAD52 inactivation is synthetically lethal with deficiencies in BRCA1 and PALB2 in addition to BRCA2 through RAD51-mediated homologous recombination.
Lok BH, Carley AC, Tchang B, Powell SN.
Oncogene. 2013 Jul 25;32(30):3552-8. doi: 10.1038/onc.2012.391. Epub 2012 Sep 10.
PMID 22964643
Molecular pathways: understanding the role of Rad52 in homologous recombination for therapeutic advancement.
Lok BH, Powell SN.
Clin Cancer Res. 2012 Dec 1;18(23):6400-6. doi: 10.1158/1078-0432.CCR-11-3150. Epub 2012 Oct 15. (REVIEW)
PMID 23071261
Double-strand break repair in the absence of RAD51 in yeast: a possible role for break-induced DNA replication.
Malkova A, Ivanov EL, Haber JE.
Proc Natl Acad Sci U S A. 1996 Jul 9;93(14):7131-6.
PMID 8692957
Break-induced replication and recombinational telomere elongation in yeast.
McEachern MJ, Haber JE.
Annu Rev Biochem. 2006;75:111-35. (REVIEW)
PMID 16756487
Dominant negative alleles of RAD52 reveal a DNA repair/recombination complex including Rad51 and Rad52.
Milne GT, Weaver DT.
Genes Dev. 1993 Sep;7(9):1755-65.
PMID 8370524
DNA strand annealing is promoted by the yeast Rad52 protein.
Mortensen UH, Bendixen C, Sunjevaric I, Rothstein R.
Proc Natl Acad Sci U S A. 1996 Oct 1;93(20):10729-34.
PMID 8855248
Human RAD52 exhibits two modes of self-association.
Ranatunga W, Jackson D, Lloyd JA, Forget AL, Knight KL, Borgstahl GE.
J Biol Chem. 2001 May 11;276(19):15876-80. Epub 2001 Feb 13.
PMID 11278978
Germline mutations in RAD51, RAD51AP1, RAD51B, RAD51C,RAD51D, RAD52 and RAD54L do not contribute to familial chronic lymphocytic leukemia.
Sellick G, Fielding S, Qureshi M, Catovsky D; International Familial CLL Consortium, Houlston R.
Leuk Lymphoma. 2008 Jan;49(1):130-3. doi: 10.1080/10428190701606800.
PMID 18203022
RAD52 variants predict platinum resistance and prognosis of cervical cancer.
Shi TY, Yang G, Tu XY, Yang JM, Qian J, Wu XH, Zhou XY, Cheng X, Wei Q.
PLoS One. 2012;7(11):e50461. doi: 10.1371/journal.pone.0050461. Epub 2012 Nov 29.
PMID 23209746
Rad52 forms ring structures and co-operates with RPA in single-strand DNA annealing.
Shinohara A, Shinohara M, Ohta T, Matsuda S, Ogawa T.
Genes Cells. 1998 Mar;3(3):145-56.
PMID 9619627
Structure of the single-strand annealing domain of human RAD52 protein.
Singleton MR, Wentzell LM, Liu Y, West SC, Wigley DB.
Proc Natl Acad Sci U S A. 2002 Oct 15;99(21):13492-7. Epub 2002 Oct 7.
PMID 12370410
The human Rad52 protein exists as a heptameric ring.
Stasiak AZ, Larquet E, Stasiak A, Muller S, Engel A, Van Dyck E, West SC, Egelman EH.
Curr Biol. 2000 Mar 23;10(6):337-40.
PMID 10744977
Rad52-mediated DNA annealing after Rad51-mediated DNA strand exchange promotes second ssDNA capture.
Sugiyama T, Kantake N, Wu Y, Kowalczykowski SC.
EMBO J. 2006 Nov 29;25(23):5539-48. Epub 2006 Nov 9.
PMID 17093500
Role of RAD52 epistasis group genes in homologous recombination and double-strand break repair.
Symington LS.
Microbiol Mol Biol Rev. 2002 Dec;66(4):630-70, table of contents. (REVIEW)
PMID 12456786
Cells expressing murine RAD52 splice variants favor sister chromatid repair.
Thorpe PH, Marrero VA, Savitzky MH, Sunjevaric I, Freeman TC, Rothstein R.
Mol Cell Biol. 2006 May;26(10):3752-63.
PMID 16648471
Rad52 gene mutations in breast/ovarian cancer families and sporadic ovarian carcinoma patients.
Tong D, Volm T, Eberhardt E, Krainer M, Leodolter S, Kreienberg R, Zeillinger R.
Oncol Rep. 2003 Sep-Oct;10(5):1551-3.
PMID 12883740
Binding of double-strand breaks in DNA by human Rad52 protein.
Van Dyck E, Stasiak AZ, Stasiak A, West SC.
Nature. 1999 Apr 22;398(6729):728-31.
PMID 10227297


This paper should be referenced as such :
BH Lok, SN Powell. RAD52 (RAD52 homolog (S
Atlas Genet Cytogenet Oncol Haematol. 2014;18(10):731-736.
Free journal version : [ pdf ]   [ DOI ]

Other Solid tumors implicated (Data extracted from papers in the Atlas) [ 1 ]
  WNK1/RAD52 (12p13)

External links

HGNC (Hugo)RAD52   9824
Entrez_Gene (NCBI)RAD52    "RAD52 homolog, DNA repair protein"
GeneCards (Weizmann)RAD52
Ensembl hg19 (Hinxton)ENSG00000002016 [Gene_View]
Ensembl hg38 (Hinxton)ENSG00000002016 [Gene_View]  ENSG00000002016 [Sequence]  chr12:911736-949694 [Contig_View]  RAD52 [Vega]
ICGC DataPortalENSG00000002016
TCGA cBioPortalRAD52
AceView (NCBI)RAD52
Genatlas (Paris)RAD52
SOURCE (Princeton)RAD52
Genetics Home Reference (NIH)RAD52
Genomic and cartography
GoldenPath hg38 (UCSC)RAD52  -     chr12:911736-949694 -  12p13.33   [Description]    (hg38-Dec_2013)
GoldenPath hg19 (UCSC)RAD52  -     12p13.33   [Description]    (hg19-Feb_2009)
GoldenPathRAD52 - 12p13.33 [CytoView hg19]  RAD52 - 12p13.33 [CytoView hg38]
genome Data Viewer NCBIRAD52 [Mapview hg19]  
Gene and transcription
Genbank (Entrez)AA402047 AF125948 AF125949 AF125950 AK290047
RefSeq transcript (Entrez)NM_001297419 NM_001297420 NM_001297421 NM_001297422 NM_134422 NM_134423 NM_134424
RefSeq genomic (Entrez)
Consensus coding sequences : CCDS (NCBI)RAD52
Alternative Splicing GalleryENSG00000002016
Gene ExpressionRAD52 [ NCBI-GEO ]   RAD52 [ EBI - ARRAY_EXPRESS ]   RAD52 [ SEEK ]   RAD52 [ MEM ]
Gene Expression Viewer (FireBrowse)RAD52 [ Firebrowse - Broad ]
GenevisibleExpression of RAD52 in : [tissues]  [cell-lines]  [cancer]  [perturbations]  
BioGPS (Tissue expression)5893
GTEX Portal (Tissue expression)RAD52
Human Protein AtlasENSG00000002016-RAD52 [pathology]   [cell]   [tissue]
Protein : pattern, domain, 3D structure
UniProt/SwissProtP43351   [function]  [subcellular_location]  [family_and_domains]  [pathology_and_biotech]  [ptm_processing]  [expression]  [interaction]
NextProtP43351  [Sequence]  [Exons]  [Medical]  [Publications]
With graphics : InterProP43351
Splice isoforms : SwissVarP43351
Domains : Interpro (EBI)DNA_recomb/repair_Rad52    Rad52_fam    Rad52_Rad59_Rad22    Rad52_Rad59_Rad22_sf   
Domain families : Pfam (Sanger)Rad52_Rad22 (PF04098)   
Domain families : Pfam (NCBI)pfam04098   
Conserved Domain (NCBI)RAD52
Blocks (Seattle)RAD52
PDB (RSDB)1H2I    1KN0    5JRB    5XRZ    5XS0   
PDB Europe1H2I    1KN0    5JRB    5XRZ    5XS0   
PDB (PDBSum)1H2I    1KN0    5JRB    5XRZ    5XS0   
PDB (IMB)1H2I    1KN0    5JRB    5XRZ    5XS0   
Structural Biology KnowledgeBase1H2I    1KN0    5JRB    5XRZ    5XS0   
SCOP (Structural Classification of Proteins)1H2I    1KN0    5JRB    5XRZ    5XS0   
CATH (Classification of proteins structures)1H2I    1KN0    5JRB    5XRZ    5XS0   
Human Protein Atlas [tissue]ENSG00000002016-RAD52 [tissue]
Peptide AtlasP43351
IPIIPI00301078   IPI00098913   IPI00852661   IPI00792549   IPI01013405   IPI00794262   IPI00028870   
Protein Interaction databases
IntAct (EBI)P43351
Ontologies - Pathways
Ontology : AmiGOdouble-strand break repair via homologous recombination  DNA recombinase assembly  DNA binding  single-stranded DNA binding  protein binding  nucleus  nucleus  nucleoplasm  double-strand break repair  DNA recombination  mitotic recombination  cellular response to DNA damage stimulus  DNA double-strand break processing involved in repair via single-strand annealing  protein-containing complex  protein-DNA complex  cellular response to oxidative stress  identical protein binding  double-strand break repair via single-strand annealing  regulation of nucleotide-excision repair  
Ontology : EGO-EBIdouble-strand break repair via homologous recombination  DNA recombinase assembly  DNA binding  single-stranded DNA binding  protein binding  nucleus  nucleus  nucleoplasm  double-strand break repair  DNA recombination  mitotic recombination  cellular response to DNA damage stimulus  DNA double-strand break processing involved in repair via single-strand annealing  protein-containing complex  protein-DNA complex  cellular response to oxidative stress  identical protein binding  double-strand break repair via single-strand annealing  regulation of nucleotide-excision repair  
Pathways : KEGGHomologous recombination   
REACTOMEP43351 [protein]
REACTOME PathwaysR-HSA-5685938 [pathway]   
NDEx NetworkRAD52
Atlas of Cancer Signalling NetworkRAD52
Wikipedia pathwaysRAD52
Orthology - Evolution
GeneTree (enSembl)ENSG00000002016
Phylogenetic Trees/Animal Genes : TreeFamRAD52
Homologs : HomoloGeneRAD52
Homology/Alignments : Family Browser (UCSC)RAD52
Gene fusions - Rearrangements
Fusion : MitelmanWNK1/RAD52 [12p13.33/12p13.33]  
Fusion PortalWNK1 12p13.33 RAD52 12p13.33 LUAD
Fusion : Fusion_HubARHGEF10--RAD52    CPSF6--RAD52    KDM5A--RAD52    NPTXR--RAD52    RAD52--CHD4    RAD52--COL6A3    RAD52--EIF4G3    RAD52--NOL10    RAD52--RASSF8    RAD52--RIMKLB    RAD52--SMIM7    RAD52--WNK1    RAD52--XPC    SRCAP--RAD52    WDR33--RAD52   
WNK1--RAD52    WRB--RAD52    ZNF664--RAD52   
Fusion : QuiverRAD52
Polymorphisms : SNP and Copy number variants
NCBI Variation ViewerRAD52 [hg38]
Exome Variant ServerRAD52
GNOMAD BrowserENSG00000002016
Varsome BrowserRAD52
Genomic Variants (DGV)RAD52 [DGVbeta]
DECIPHERRAD52 [patients]   [syndromes]   [variants]   [genes]  
CONAN: Copy Number AnalysisRAD52 
ICGC Data PortalRAD52 
TCGA Data PortalRAD52 
Broad Tumor PortalRAD52
OASIS PortalRAD52 [ Somatic mutations - Copy number]
Somatic Mutations in Cancer : COSMICRAD52  [overview]  [genome browser]  [tissue]  [distribution]  
Somatic Mutations in Cancer : COSMIC3DRAD52
Mutations and Diseases : HGMDRAD52
LOVD (Leiden Open Variation Database)Whole genome datasets
LOVD (Leiden Open Variation Database)LOVD - Leiden Open Variation Database
LOVD (Leiden Open Variation Database)LOVD 3.0 shared installation
BioMutasearch RAD52
DgiDB (Drug Gene Interaction Database)RAD52
DoCM (Curated mutations)RAD52 (select the gene name)
CIViC (Clinical Interpretations of Variants in Cancer)RAD52 (select a term)
NCG6 (London) select RAD52
Cancer3DRAD52(select the gene name)
Impact of mutations[PolyPhen2] [Provean] [Buck Institute : MutDB] [Mutation Assessor] [Mutanalyser]
Genetic Testing Registry RAD52
NextProtP43351 [Medical]
Target ValidationRAD52
Huge Navigator RAD52 [HugePedia]
Clinical trials, drugs, therapy
Protein Interactions : CTD
Pharm GKB GenePA34180
Clinical trialRAD52
canSAR (ICR)RAD52 (select the gene name)
DataMed IndexRAD52
PubMed140 Pubmed reference(s) in Entrez
GeneRIFsGene References Into Functions (Entrez)
REVIEW articlesautomatic search in PubMed
Last year publicationsautomatic search in PubMed

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