Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTPCH3JH)

• DOT Name: ATP-dependent DNA helicase Q1 (RECQL)
• Synonyms: EC 5.6.2.4; DNA 3'-5' helicase Q1; DNA helicase, RecQ-like type 1; RecQ1; DNA-dependent ATPase Q1; RecQ protein-like 1
• Gene Name: RECQL
• Related Disease:
  Adult glioblastoma
  Glioblastoma multiforme
  Xeroderma pigmentosum group C
  Bone osteosarcoma
  Breast neoplasm
  Carcinoma of liver and intrahepatic biliary tract
  Cervical cancer
  Head-neck squamous cell carcinoma
  Hepatocellular carcinoma
  Laryngeal carcinoma
  Leukopenia
  Liver cancer
  Lung cancer
  Lung carcinoma
  Non-small-cell lung cancer
  Osteosarcoma
  Ovarian cancer
  Ovarian neoplasm
  Pancreatic adenocarcinoma
  Rothmund-Thomson syndrome
  Triple negative breast cancer
  Xeroderma pigmentosum
  Neoplasm
  Plasma cell myeloma
  Adenocarcinoma
  Breast cancer
  Hereditary breast carcinoma
  Kaposi sarcoma
  RECON progeroid syndrome
  Werner syndrome
  Familial ovarian cancer
• UniProt ID: RECQ1_HUMAN
• PDB ID: 2V1X; 2WWY; 4U7D; 6JTZ
• EC Number: 5.6.2.4
• Pfam ID: PF00270 ; PF00271 ; PF16124
• Sequence:
  MASVSALTEELDSITSELHAVEIQIQELTERQQELIQKKKVLTKKIKQCLEDSDAGASNE
  YDSSPAAWNKEDFPWSGKVKDILQNVFKLEKFRPLQLETINVTMAGKEVFLVMPTGGGKS
  LCYQLPALCSDGFTLVICPLISLMEDQLMVLKQLGISATMLNASSSKEHVKWVHAEMVNK
  NSELKLIYVTPEKIAKSKMFMSRLEKAYEARRFTRIAVDEVHCCSQWGHDFRPDYKALGI
  LKRQFPNASLIGLTATATNHVLTDAQKILCIEKCFTFTASFNRPNLYYEVRQKPSNTEDF
  IEDIVKLINGRYKGQSGIIYCFSQKDSEQVTVSLQNLGIHAGAYHANLEPEDKTTVHRKW
  SANEIQVVVATVAFGMGIDKPDVRFVIHHSMSKSMENYYQESGRAGRDDMKADCILYYGF
  GDIFRISSMVVMENVGQQKLYEMVSYCQNISKCRRVLMAQHFDEVWNSEACNKMCDNCCK
  DSAFERKNITEYCRDLIKILKQAEELNEKLTPLKLIDSWMGKGAAKLRVAGVVAPTLPRE
  DLEKIIAHFLIQQYLKEDYSFTAYATISYLKIGPKANLLNNEAHAITMQVTKSTQNSFRA
  ESSQTCHSEQGDKKMEEKNSGNFQKKAANMLQQSGSKNTGAKKRKIDDA
• Function: DNA helicase that plays a role in DNA damage repair and genome stability. Exhibits a magnesium- and ATP-dependent DNA-helicase activity that unwinds single- and double-stranded DNA in a 3'-5' direction. Full-length protein unwinds forked DNA substrates, resolves Holliday junctions, and has DNA strand annealing activity. Plays a role in restoring regressed replication forks. Required to restart stalled replication forks induced by abortive topoisomerase 1 and 2 lesions. May play a role in the repair of DNA that is damaged by ultraviolet light or other mutagens.
• Tissue Specificity: High expression in heart, lung, skeletal muscle and kidney, low expression in brain.

Molecular Interaction Atlas (MIA) of This DOT

31 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Adult glioblastoma	DISVP4LU	Definitive	Biomarker	[1]
Glioblastoma multiforme	DISK8246	Definitive	Biomarker	[1]
Xeroderma pigmentosum group C	DIS8DQXS	Definitive	Biomarker	[2]
Bone osteosarcoma	DIST1004	Strong	Genetic Variation	[3]
Breast neoplasm	DISNGJLM	Strong	Biomarker	[4]
Carcinoma of liver and intrahepatic biliary tract	DIS8WA0W	Strong	Biomarker	[5]
Cervical cancer	DISFSHPF	Strong	Biomarker	[6]
Head-neck squamous cell carcinoma	DISF7P24	Strong	Biomarker	[7]
Hepatocellular carcinoma	DIS0J828	Strong	Biomarker	[5]
Laryngeal carcinoma	DISNHCIV	Strong	Genetic Variation	[8]
Leukopenia	DISJMBMM	Strong	Genetic Variation	[9]
Liver cancer	DISDE4BI	Strong	Biomarker	[5]
Lung cancer	DISCM4YA	Strong	Biomarker	[6]
Lung carcinoma	DISTR26C	Strong	Biomarker	[6]
Non-small-cell lung cancer	DIS5Y6R9	Strong	Altered Expression	[6]
Osteosarcoma	DISLQ7E2	Strong	Genetic Variation	[3]
Ovarian cancer	DISZJHAP	Strong	Genetic Variation	[10]
Ovarian neoplasm	DISEAFTY	Strong	Genetic Variation	[10]
Pancreatic adenocarcinoma	DISKHX7S	Strong	Biomarker	[11]
Rothmund-Thomson syndrome	DISGVBCV	Strong	Genetic Variation	[12]
Triple negative breast cancer	DISAMG6N	Strong	Biomarker	[13]
Xeroderma pigmentosum	DISQ9H19	Strong	Biomarker	[14]
Neoplasm	DISZKGEW	moderate	Altered Expression	[15]
Plasma cell myeloma	DIS0DFZ0	moderate	Biomarker	[16]
Adenocarcinoma	DIS3IHTY	Disputed	Altered Expression	[17]
Breast cancer	DIS7DPX1	Disputed	Autosomal dominant	[18]
Hereditary breast carcinoma	DISAEZT5	Disputed	Autosomal dominant	[19]
Kaposi sarcoma	DISC1H1Z	Limited	Genetic Variation	[20]
RECON progeroid syndrome	DIS80UQ8	Limited	Autosomal recessive	[21]
Werner syndrome	DISZY45W	Limited	Genetic Variation	[22]
Familial ovarian cancer	DISGLR2C	No Known	Autosomal dominant	[19]

13 Drug(s) Affected the Gene/Protein Processing of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the expression of ATP-dependent DNA helicase Q1 (RECQL).	[23]
Ciclosporin	DMAZJFX	Approved	Ciclosporin affects the expression of ATP-dependent DNA helicase Q1 (RECQL).	[24]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of ATP-dependent DNA helicase Q1 (RECQL).	[25]
Estradiol	DMUNTE3	Approved	Estradiol affects the expression of ATP-dependent DNA helicase Q1 (RECQL).	[26]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of ATP-dependent DNA helicase Q1 (RECQL).	[27]
Quercetin	DM3NC4M	Approved	Quercetin increases the expression of ATP-dependent DNA helicase Q1 (RECQL).	[29]
Selenium	DM25CGV	Approved	Selenium decreases the expression of ATP-dependent DNA helicase Q1 (RECQL).	[30]
Piroxicam	DMTK234	Approved	Piroxicam decreases the expression of ATP-dependent DNA helicase Q1 (RECQL).	[31]
Tocopherol	DMBIJZ6	Phase 2	Tocopherol decreases the expression of ATP-dependent DNA helicase Q1 (RECQL).	[30]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of ATP-dependent DNA helicase Q1 (RECQL).	[32]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of ATP-dependent DNA helicase Q1 (RECQL).	[33]
Acetaldehyde	DMJFKG4	Investigative	Acetaldehyde decreases the expression of ATP-dependent DNA helicase Q1 (RECQL).	[34]
KOJIC ACID	DMP84CS	Investigative	KOJIC ACID decreases the expression of ATP-dependent DNA helicase Q1 (RECQL).	[35]

1 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of ATP-dependent DNA helicase Q1 (RECQL).	[28]

References

• [1] RECQ1 Helicase Silencing Decreases the Tumour Growth Rate of U87 Glioblastoma Cell Xenografts in Zebrafish Embryos.Genes (Basel). 2017 Sep 6;8(9):222. doi: 10.3390/genes8090222.
• [2] Characterization of the properties of a human homologue of Escherichia coli RecQ from xeroderma pigmentosum group C and from HeLa cells.Cell Struct Funct. 1996 Apr;21(2):123-32. doi: 10.1247/csf.21.123.
• [3] Single nucleotide polymorphism in the RECQL5 gene increased osteosarcoma susceptibility in a Chinese Han population.Genet Mol Res. 2015 Mar 13;14(1):1899-902. doi: 10.4238/2015.March.13.18.
• [4] Germline RECQL mutations are associated with breast cancer susceptibility.Nat Genet. 2015 Jun;47(6):643-6. doi: 10.1038/ng.3284. Epub 2015 Apr 27.
• [5] RecQL1 DNA repair helicase: A potential tumor marker and therapeutic target against hepatocellular carcinoma.Int J Mol Med. 2010 Apr;25(4):537-45. doi: 10.3892/ijmm_00000375.
• [6] Effects of RECQ1 helicase silencing on non-small cell lung cancer cells.Biomed Pharmacother. 2016 Oct;83:1227-1232. doi: 10.1016/j.biopha.2016.07.053. Epub 2016 Aug 23.
• [7] RECQL1 and WRN proteins are potential therapeutic targets in head and neck squamous cell carcinoma.Cancer Res. 2011 Jul 1;71(13):4598-607. doi: 10.1158/0008-5472.CAN-11-0320. Epub 2011 May 13.
• [8] Haplotype analysis of RECQL5 gene and laryngeal cancer.Tumour Biol. 2014 Mar;35(3):2669-73. doi: 10.1007/s13277-013-1351-5. Epub 2013 Nov 9.
• [9] Germline polymorphisms in patients with advanced nonsmall cell lung cancer receiving first-line platinum-gemcitabine chemotherapy: a prospective clinical study.Cancer. 2012 May 1;118(9):2466-75. doi: 10.1002/cncr.26562. Epub 2011 Sep 28.
• [10] FANCM and RECQL genetic variants and breast cancer susceptibility: relevance to South Poland and West Ukraine.BMC Med Genet. 2018 Jan 19;19(1):12. doi: 10.1186/s12881-018-0524-x.
• [11] DNA repair gene polymorphisms and risk of pancreatic cancer.Clin Cancer Res. 2009 Jan 15;15(2):740-6. doi: 10.1158/1078-0432.CCR-08-1607.
• [12] Molecular defect of RAPADILINO syndrome expands the phenotype spectrum of RECQL diseases. Hum Mol Genet. 2003 Nov 1;12(21):2837-44. doi: 10.1093/hmg/ddg306. Epub 2003 Sep 2.
• [13] The DNA repair helicase RECQ1 has a checkpoint-dependent role in mediating DNA damage responses induced by gemcitabine.J Biol Chem. 2019 Oct 18;294(42):15330-15345. doi: 10.1074/jbc.RA119.008420. Epub 2019 Aug 23.
• [14] Alteration of a DNA-dependent ATPase activity in xeroderma pigmentosum complementation group C cells.J Biol Chem. 1992 Feb 25;267(6):3585-8.
• [15] Clinicopathological and Functional Significance of RECQL1 Helicase in Sporadic Breast Cancers.Mol Cancer Ther. 2017 Jan;16(1):239-250. doi: 10.1158/1535-7163.MCT-16-0290. Epub 2016 Nov 11.
• [16] RECQ1 helicase is involved in replication stress survival and drug resistance in multiple myeloma.Leukemia. 2017 Oct;31(10):2104-2113. doi: 10.1038/leu.2017.54. Epub 2017 Feb 10.
• [17] RECQL1 DNA repair helicase: a potential therapeutic target and a proliferative marker against ovarian cancer.PLoS One. 2013 Aug 9;8(8):e72820. doi: 10.1371/journal.pone.0072820. eCollection 2013.
• [18] Classification of Genes: Standardized Clinical Validity Assessment of Gene-Disease Associations Aids Diagnostic Exome Analysis and Reclassifications. Hum Mutat. 2017 May;38(5):600-608. doi: 10.1002/humu.23183. Epub 2017 Feb 13.
• [19] Technical standards for the interpretation and reporting of constitutional copy-number variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics (ACMG) and the Clinical Genome Resource (ClinGen). Genet Med. 2020 Feb;22(2):245-257. doi: 10.1038/s41436-019-0686-8. Epub 2019 Nov 6.
• [20] Topoisomerase I and RecQL1 function in Epstein-Barr virus lytic reactivation.J Virol. 2009 Aug;83(16):8090-8. doi: 10.1128/JVI.02379-08. Epub 2009 Jun 3.
• [21] RECON syndrome is a genome instability disorder caused by mutations in the DNA helicase RECQL1. J Clin Invest. 2022 Mar 1;132(5):e147301. doi: 10.1172/JCI147301.
• [22] Ectopic hTERT expression facilitates reprograming of fibroblasts derived from patients with Werner syndrome as a WS cellular model.Cell Death Dis. 2018 Sep 11;9(9):923. doi: 10.1038/s41419-018-0948-4.
• [23] Integrative omics data analyses of repeated dose toxicity of valproic acid in vitro reveal new mechanisms of steatosis induction. Toxicology. 2018 Jan 15;393:160-170.
• [24] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [25] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [26] Identification of novel low-dose bisphenol a targets in human foreskin fibroblast cells derived from hypospadias patients. PLoS One. 2012;7(5):e36711. doi: 10.1371/journal.pone.0036711. Epub 2012 May 4.
• [27] Quantitative proteomics reveals a broad-spectrum antiviral property of ivermectin, benefiting for COVID-19 treatment. J Cell Physiol. 2021 Apr;236(4):2959-2975. doi: 10.1002/jcp.30055. Epub 2020 Sep 22.
• [28] Prenatal arsenic exposure and the epigenome: identifying sites of 5-methylcytosine alterations that predict functional changes in gene expression in newborn cord blood and subsequent birth outcomes. Toxicol Sci. 2015 Jan;143(1):97-106. doi: 10.1093/toxsci/kfu210. Epub 2014 Oct 10.
• [29] Comparison of phenotypic and transcriptomic effects of false-positive genotoxins, true genotoxins and non-genotoxins using HepG2 cells. Mutagenesis. 2011 Sep;26(5):593-604.
• [30] Selenium and vitamin E: cell type- and intervention-specific tissue effects in prostate cancer. J Natl Cancer Inst. 2009 Mar 4;101(5):306-20.
• [31] Apoptosis induced by piroxicam plus cisplatin combined treatment is triggered by p21 in mesothelioma. PLoS One. 2011;6(8):e23569.
• [32] Cell-based two-dimensional morphological assessment system to predict cancer drug-induced cardiotoxicity using human induced pluripotent stem cell-derived cardiomyocytes. Toxicol Appl Pharmacol. 2019 Nov 15;383:114761. doi: 10.1016/j.taap.2019.114761. Epub 2019 Sep 15.
• [33] Characterization of the Molecular Alterations Induced by the Prolonged Exposure of Normal Colon Mucosa and Colon Cancer Cells to Low-Dose Bisphenol A. Int J Mol Sci. 2022 Oct 1;23(19):11620. doi: 10.3390/ijms231911620.
• [34] Transcriptome profile analysis of saturated aliphatic aldehydes reveals carbon number-specific molecules involved in pulmonary toxicity. Chem Res Toxicol. 2014 Aug 18;27(8):1362-70.
• [35] Toxicogenomics of kojic acid on gene expression profiling of a375 human malignant melanoma cells. Biol Pharm Bull. 2006 Apr;29(4):655-69.