Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT0OTDHI)

DOT Name DNA repair protein RAD52 homolog (RAD52)
Gene Name RAD52
Related Disease
Cervical cancer ( )
Cervical carcinoma ( )
Adenocarcinoma ( )
Advanced cancer ( )
Alzheimer disease ( )
Breast neoplasm ( )
Cockayne syndrome ( )
Colorectal carcinoma ( )
Differentiated thyroid carcinoma ( )
Fanconi anemia complementation group A ( )
Fanconi's anemia ( )
Giardiasis ( )
Glioma ( )
Head and neck cancer ( )
Head and neck carcinoma ( )
Hepatitis B virus infection ( )
leukaemia ( )
Leukemia ( )
Lung adenocarcinoma ( )
Lung carcinoma ( )
Lung neoplasm ( )
Lung squamous cell carcinoma ( )
Myelodysplastic syndrome ( )
Neoplasm ( )
Nijmegen breakage syndrome ( )
Non-small-cell lung cancer ( )
Polyarteritis nodosa ( )
Salivary gland carcinoma ( )
Squamous cell carcinoma ( )
Thyroid cancer ( )
Thyroid gland carcinoma ( )
Thyroid gland papillary carcinoma ( )
Thyroid tumor ( )
Vasculitis due to ADA2 deficiency ( )
Carcinoma ( )
Hepatocellular carcinoma ( )
Ovarian cancer ( )
Ovarian neoplasm ( )
Neuroblastoma ( )
Breast cancer ( )
Breast carcinoma ( )
Lung cancer ( )
Small lymphocytic lymphoma ( )
UniProt ID
RAD52_HUMAN
3D Structure
Download
2D Sequence (FASTA)
Download
3D Structure (PDB)
Download
PDB ID
1H2I; 1KN0; 5JRB; 5XRZ; 5XS0; 8BJM; 8H1P
Pfam ID
PF04098
Sequence
MSGTEEAILGGRDSHPAAGGGSVLCFGQCQYTAEEYQAIQKALRQRLGPEYISSRMAGGG
QKVCYIEGHRVINLANEMFGYNGWAHSITQQNVDFVDLNNGKFYVGVCAFVRVQLKDGSY
HEDVGYGVSEGLKSKALSLEKARKEAVTDGLKRALRSFGNALGNCILDKDYLRSLNKLPR
QLPLEVDLTKAKRQDLEPSVEEARYNSCRPNMALGHPQLQQVTSPSRPSHAVIPADQDCS
SRSLSSSAVESEATHQRKLRQKQLQQQFRERMEKQQVRVSTPSAEKSEAAPPAPPVTHST
PVTVSEPLLEKDFLAGVTQELIKTLEDNSEKWAVTPDAGDGVVKPSSRADPAQTSDTLAL
NNQMVTQNRTPHSVCHQKPQAKSGSWDLQTYSADQRTTGNWESHRKSQDMKKRKYDPS
Function
Involved in double-stranded break repair. Plays a central role in genetic recombination and DNA repair by promoting the annealing of complementary single-stranded DNA and by stimulation of the RAD51 recombinase.
KEGG Pathway
Homologous recombi.tion (hsa03440 )
Reactome Pathway
HDR through Single Strand Annealing (SSA) (R-HSA-5685938 )
HDR through MMEJ (alt-NHEJ) (R-HSA-5685939 )
SUMOylation of DNA damage response and repair proteins (R-HSA-3108214 )

Molecular Interaction Atlas (MIA) of This DOT

43 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Cervical cancer DISFSHPF Definitive Genetic Variation [1]
Cervical carcinoma DIST4S00 Definitive Genetic Variation [1]
Adenocarcinoma DIS3IHTY Strong Biomarker [2]
Advanced cancer DISAT1Z9 Strong Biomarker [3]
Alzheimer disease DISF8S70 Strong Altered Expression [4]
Breast neoplasm DISNGJLM Strong Genetic Variation [5]
Cockayne syndrome DISW6GL2 Strong Biomarker [6]
Colorectal carcinoma DIS5PYL0 Strong Genetic Variation [7]
Differentiated thyroid carcinoma DIS1V20Y Strong Genetic Variation [8]
Fanconi anemia complementation group A DIS8PZLI Strong Biomarker [9]
Fanconi's anemia DISGW6Q8 Strong Biomarker [9]
Giardiasis DISWUNWK Strong Biomarker [10]
Glioma DIS5RPEH Strong Genetic Variation [11]
Head and neck cancer DISBPSQZ Strong Genetic Variation [12]
Head and neck carcinoma DISOU1DS Strong Genetic Variation [12]
Hepatitis B virus infection DISLQ2XY Strong Biomarker [13]
leukaemia DISS7D1V Strong Altered Expression [14]
Leukemia DISNAKFL Strong Altered Expression [14]
Lung adenocarcinoma DISD51WR Strong Genetic Variation [15]
Lung carcinoma DISTR26C Strong Biomarker [2]
Lung neoplasm DISVARNB Strong Biomarker [16]
Lung squamous cell carcinoma DISXPIBD Strong Altered Expression [17]
Myelodysplastic syndrome DISYHNUI Strong Biomarker [18]
Neoplasm DISZKGEW Strong Biomarker [19]
Nijmegen breakage syndrome DIS98HVL Strong Biomarker [20]
Non-small-cell lung cancer DIS5Y6R9 Strong Biomarker [21]
Polyarteritis nodosa DISRQ5X8 Strong Altered Expression [22]
Salivary gland carcinoma DISLVGGG Strong Genetic Variation [23]
Squamous cell carcinoma DISQVIFL Strong Biomarker [2]
Thyroid cancer DIS3VLDH Strong Genetic Variation [24]
Thyroid gland carcinoma DISMNGZ0 Strong Genetic Variation [24]
Thyroid gland papillary carcinoma DIS48YMM Strong Genetic Variation [24]
Thyroid tumor DISLVKMD Strong Genetic Variation [24]
Vasculitis due to ADA2 deficiency DIS1UHPY Strong Altered Expression [22]
Carcinoma DISH9F1N moderate Altered Expression [25]
Hepatocellular carcinoma DIS0J828 moderate Altered Expression [26]
Ovarian cancer DISZJHAP moderate Biomarker [27]
Ovarian neoplasm DISEAFTY moderate Biomarker [27]
Neuroblastoma DISVZBI4 Disputed Biomarker [28]
Breast cancer DIS7DPX1 Limited Biomarker [29]
Breast carcinoma DIS2UE88 Limited Biomarker [29]
Lung cancer DISCM4YA Limited Biomarker [2]
Small lymphocytic lymphoma DIS30POX Limited Genetic Variation [30]
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⏷ Show the Full List of 43 Disease(s)
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
2 Drug(s) Affected the Gene/Protein Processing of This DOT
Drug Name Drug ID Highest Status Interaction REF
Valproate DMCFE9I Approved Valproate decreases the expression of DNA repair protein RAD52 homolog (RAD52). [31]
Etoposide DMNH3PG Approved Etoposide increases the expression of DNA repair protein RAD52 homolog (RAD52). [33]
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3 Drug(s) Affected the Post-Translational Modifications of This DOT
Drug Name Drug ID Highest Status Interaction REF
Ciclosporin DMAZJFX Approved Ciclosporin increases the methylation of DNA repair protein RAD52 homolog (RAD52). [32]
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene increases the methylation of DNA repair protein RAD52 homolog (RAD52). [34]
Bisphenol A DM2ZLD7 Investigative Bisphenol A affects the methylation of DNA repair protein RAD52 homolog (RAD52). [35]
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References

1 RAD52 variants predict platinum resistance and prognosis of cervical cancer.PLoS One. 2012;7(11):e50461. doi: 10.1371/journal.pone.0050461. Epub 2012 Nov 29.
2 Genome-wide association study of familial lung cancer.Carcinogenesis. 2018 Sep 21;39(9):1135-1140. doi: 10.1093/carcin/bgy080.
3 Human RAD52 protein regulates homologous recombination and checkpoint function in BRCA2 deficient cells.Int J Biochem Cell Biol. 2019 Feb;107:128-139. doi: 10.1016/j.biocel.2018.12.013. Epub 2018 Dec 24.
4 RAD52 is required for RNA-templated recombination repair in post-mitotic neurons.J Biol Chem. 2018 Jan 26;293(4):1353-1362. doi: 10.1074/jbc.M117.808402. Epub 2017 Dec 7.
5 No association between a stop codon polymorphism in RAD52 and breast cancer risk.Cancer Epidemiol Biomarkers Prev. 2002 Oct;11(10 Pt 1):1138-9.
6 ROS-induced R loops trigger a transcription-coupled but BRCA1/2-independent homologous recombination pathway through CSB.Nat Commun. 2018 Oct 8;9(1):4115. doi: 10.1038/s41467-018-06586-3.
7 RAD52 gene polymorphisms are associated with risk of colorectal cancer in a Chinese Han population.Medicine (Baltimore). 2017 Dec;96(49):e8994. doi: 10.1097/MD.0000000000008994.
8 Increased risk of differentiated thyroid carcinoma with combined effects of homologous recombination repair gene polymorphisms in an Iranian population.Asian Pac J Cancer Prev. 2014 Jan;14(11):6727-31. doi: 10.7314/apjcp.2013.14.11.6727.
9 FANCA Promotes DNA Double-Strand Break Repair by Catalyzing Single-Strand Annealing and Strand Exchange.Mol Cell. 2018 Aug 16;71(4):621-628.e4. doi: 10.1016/j.molcel.2018.06.030. Epub 2018 Jul 26.
10 Giardia duodenalis Rad52 protein: biochemical characterization and response upon DNA damage.J Biochem. 2017 Aug 1;162(2):123-135. doi: 10.1093/jb/mvx009.
11 A RAD52 genetic variant located in a miRNA binding site is associated with glioma risk in Han Chinese.J Neurooncol. 2014 Oct;120(1):11-7. doi: 10.1007/s11060-014-1527-x. Epub 2014 Jul 11.
12 Assessment of DNA repair susceptibility genes identified by whole exome sequencing in head and neck cancer.DNA Repair (Amst). 2018 Jun-Jul;66-67:50-63. doi: 10.1016/j.dnarep.2018.04.005. Epub 2018 Apr 26.
13 Association of a functional RAD52 genetic variant locating in a miRNA binding site with risk of HBV-related hepatocellular carcinoma.Mol Carcinog. 2015 Sep;54(9):853-8. doi: 10.1002/mc.22156. Epub 2014 Apr 11.
14 Simultaneous Targeting of PARP1 and RAD52 Triggers Dual Synthetic Lethality in BRCA-Deficient Tumor Cells.Cell Rep. 2018 Jun 12;23(11):3127-3136. doi: 10.1016/j.celrep.2018.05.034.
15 Characteristics of genomic alterations of lung adenocarcinoma in young never-smokers.Int J Cancer. 2018 Oct 1;143(7):1696-1705. doi: 10.1002/ijc.31542. Epub 2018 May 7.
16 Functional characterization of RAD52 as a lung cancer susceptibility gene in the 12p13.33 locus.Mol Carcinog. 2016 May;55(5):953-63. doi: 10.1002/mc.22334. Epub 2015 May 27.
17 The 12p13.33/RAD52 locus and genetic susceptibility to squamous cell cancers of upper aerodigestive tract.PLoS One. 2015 Mar 20;10(3):e0117639. doi: 10.1371/journal.pone.0117639. eCollection 2015.
18 DNA repair gene variants are associated with an increased risk of myelodysplastic syndromes in a Czech population.J Hematol Oncol. 2013 Jan 22;6:9. doi: 10.1186/1756-8722-6-9.
19 Distinct roles of RAD52 and POLQ in chromosomal break repair and replication stress response.PLoS Genet. 2019 Aug 5;15(8):e1008319. doi: 10.1371/journal.pgen.1008319. eCollection 2019 Aug.
20 Nijmegen breakage syndrome gene (NBS1) is not the tumor suppressor gene at 8q21.3 involved in colorectal carcinoma.Oncol Rep. 2002 Jul-Aug;9(4):709-11.
21 RAD52 motifcontaining protein1 promotes nonsmall cell lung cancer cell proliferation and survival via cell cycle regulation.Oncol Rep. 2018 Aug;40(2):833-840. doi: 10.3892/or.2018.6459. Epub 2018 May 23.
22 Human somatic cells deficient for RAD52 are impaired for viral integration and compromised for most aspects of homology-directed repair.DNA Repair (Amst). 2017 Jul;55:64-75. doi: 10.1016/j.dnarep.2017.04.006. Epub 2017 May 10.
23 Genetic variants in DNA double-strand break repair genes and risk of salivary gland carcinoma: a case-control study.PLoS One. 2015 Jun 2;10(6):e0128753. doi: 10.1371/journal.pone.0128753. eCollection 2015.
24 RAD52 polymorphisms contribute to the development of papillary thyroid cancer susceptibility in Middle Eastern population.J Endocrinol Invest. 2008 Oct;31(10):893-9. doi: 10.1007/BF03346438.
25 Identification of a Small Molecule Inhibitor of RAD52 by Structure-Based Selection.PLoS One. 2016 Jan 19;11(1):e0147230. doi: 10.1371/journal.pone.0147230. eCollection 2016.
26 Evaluating the role of RAD52 and its interactors as novel potential molecular targets for hepatocellular carcinoma.Cancer Cell Int. 2019 Nov 6;19:279. doi: 10.1186/s12935-019-0996-6. eCollection 2019.
27 RAD52 Y415X truncation polymorphism and epithelial ovarian cancer risk in Australian women.Cancer Lett. 2005 Feb 10;218(2):191-7. doi: 10.1016/j.canlet.2004.09.023.
28 RDM1 promotes neuroblastoma growth through the RAS-Raf-MEK-ERK pathway.FEBS Open Bio. 2019 Jan 28;9(3):490-497. doi: 10.1002/2211-5463.12586. eCollection 2019 Mar.
29 Replication Stress Response Links RAD52 to Protecting Common Fragile Sites.Cancers (Basel). 2019 Sep 29;11(10):1467. doi: 10.3390/cancers11101467.
30 Germline mutations in RAD51, RAD51AP1, RAD51B, RAD51C,RAD51D, RAD52 and RAD54L do not contribute to familial chronic lymphocytic leukemia.Leuk Lymphoma. 2008 Jan;49(1):130-3. doi: 10.1080/10428190701606800.
31 Design principles of concentration-dependent transcriptome deviations in drug-exposed differentiating stem cells. Chem Res Toxicol. 2014 Mar 17;27(3):408-20.
32 Integrative "-Omics" analysis in primary human hepatocytes unravels persistent mechanisms of cyclosporine A-induced cholestasis. Chem Res Toxicol. 2016 Dec 19;29(12):2164-2174.
33 A molecular beacon approach to detecting RAD52 expression in response to DNA damage in human cells. Toxicol In Vitro. 2010 Mar;24(2):652-60. doi: 10.1016/j.tiv.2009.09.019. Epub 2009 Sep 30.
34 Air pollution and DNA methylation alterations in lung cancer: A systematic and comparative study. Oncotarget. 2017 Jan 3;8(1):1369-1391. doi: 10.18632/oncotarget.13622.
35 Maternal environmental exposure to bisphenols and epigenome-wide DNA methylation in infant cord blood. Environ Epigenet. 2020 Dec 23;6(1):dvaa021. doi: 10.1093/eep/dvaa021. eCollection 2020.