Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTUD6SY5)

• DOT Name: DNA repair protein RAD51 homolog 3 (RAD51C)
• Synonyms: R51H3; RAD51 homolog C; RAD51-like protein 2
• Gene Name: RAD51C
• Related Disease:
  Breast-ovarian cancer, familial, susceptibility to, 3
  Advanced cancer
  Breast neoplasm
  Cleft lip/palate
  Colorectal carcinoma
  Colorectal neoplasm
  Fanconi anemia complementation group O
  Head and neck cancer
  Head and neck carcinoma
  Head-neck squamous cell carcinoma
  Lobar holoprosencephaly
  Neoplasm
  Testicular germ cell tumor
  Acute monocytic leukemia
  Acute myelogenous leukaemia
  Carcinoid tumor
  Carcinoma
  Myelodysplastic syndrome
  Pancytopenia
  Small-cell lung cancer
  Fanconi's anemia
  Hereditary breast ovarian cancer syndrome
  Hereditary breast carcinoma
  Hereditary neoplastic syndrome
  Chromosomal disorder
  Fanconi anemia complementation group A
  Hereditary nonpolyposis colon cancer
  Lynch syndrome
• UniProt ID: RA51C_HUMAN
• PDB ID: 8FAZ; 8GBJ; 8OUY; 8OUZ
• Pfam ID: PF08423
• Sequence:
  MRGKTFRFEMQRDLVSFPLSPAVRVKLVSAGFQTAEELLEVKPSELSKEVGISKAEALET
  LQIIRRECLTNKPRYAGTSESHKKCTALELLEQEHTQGFIITFCSALDDILGGGVPLMKT
  TEICGAPGVGKTQLCMQLAVDVQIPECFGGVAGEAVFIDTEGSFMVDRVVDLATACIQHL
  QLIAEKHKGEEHRKALEDFTLDNILSHIYYFRCRDYTELLAQVYLLPDFLSEHSKVRLVI
  VDGIAFPFRHDLDDLSLRTRLLNGLAQQMISLANNHRLAVILTNQMTTKIDRNQALLVPA
  LGESWGHAATIRLIFHWDRKQRLATLYKSPSQKECTVLFQIKPQGFRDTVVTSACSLQTE
  GSLSTRKRSRDPEEEL
• Function: Essential for the homologous recombination (HR) pathway of DNA repair. Involved in the homologous recombination repair (HRR) pathway of double-stranded DNA breaks arising during DNA replication or induced by DNA-damaging agents. Part of the RAD51 paralog protein complexes BCDX2 and CX3 which act at different stages of the BRCA1-BRCA2-dependent HR pathway. Upon DNA damage, BCDX2 seems to act downstream of BRCA2 recruitment and upstream of RAD51 recruitment; CX3 seems to act downstream of RAD51 recruitment; both complexes bind predominantly to the intersection of the four duplex arms of the Holliday junction (HJ) and to junction of replication forks. The BCDX2 complex was originally reported to bind single-stranded DNA, single-stranded gaps in duplex DNA and specifically to nicks in duplex DNA. The BCDX2 subcomplex RAD51B:RAD51C exhibits single-stranded DNA-dependent ATPase activity suggesting an involvement in early stages of the HR pathway. Involved in RAD51 foci formation in response to DNA damage suggesting an involvement in early stages of HR probably in the invasion step. Has an early function in DNA repair in facilitating phosphorylation of the checkpoint kinase CHEK2 and thereby transduction of the damage signal, leading to cell cycle arrest and HR activation. Participates in branch migration and HJ resolution and thus is important for processing HR intermediates late in the DNA repair process; the function may be linked to the CX3 complex. Part of a PALB2-scaffolded HR complex containing BRCA2 and which is thought to play a role in DNA repair by HR. Protects RAD51 from ubiquitin-mediated degradation that is enhanced following DNA damage. Plays a role in regulating mitochondrial DNA copy number under conditions of oxidative stress in the presence of RAD51 and XRCC3. Contributes to DNA cross-link resistance, sister chromatid cohesion and genomic stability. Involved in maintaining centrosome number in mitosis.
• Tissue Specificity: Expressed in a variety of tissues, with highest expression in testis, heart muscle, spleen and prostate.
• KEGG Pathway:
  Homologous recombi.tion (hsa03440)
  Fanconi anemia pathway (hsa03460)
• Reactome Pathway:
  Resolution of D-loop Structures through Synthesis-Dependent Strand Annealing (SDSA) (R-HSA-5693554)
  Resolution of D-loop Structures through Holliday Junction Intermediates (R-HSA-5693568)
  Homologous DNA Pairing and Strand Exchange (R-HSA-5693579)
  Presynaptic phase of homologous DNA pairing and strand exchange (R-HSA-5693616)
  Meiotic recombination (R-HSA-912446)
  Defective homologous recombination repair (HRR) due to BRCA1 loss of function (R-HSA-9701192)
  Defective HDR through Homologous Recombination Repair (HRR) due to PALB2 loss of BRCA1 binding function (R-HSA-9704331)
  Defective HDR through Homologous Recombination Repair (HRR) due to PALB2 loss of BRCA2/RAD51/RAD51C binding function (R-HSA-9704646)
  Impaired BRCA2 binding to PALB2 (R-HSA-9709603)
  Factors involved in megakaryocyte development and platelet production (R-HSA-983231)
  HDR through Homologous Recombination (HRR) (R-HSA-5685942)

Molecular Interaction Atlas (MIA) of This DOT

28 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Breast-ovarian cancer, familial, susceptibility to, 3	DISHX3FO	Definitive	Autosomal dominant	[1]
Advanced cancer	DISAT1Z9	Strong	Biomarker	[2]
Breast neoplasm	DISNGJLM	Strong	Biomarker	[2]
Cleft lip/palate	DIS14IG3	Strong	Genetic Variation	[3]
Colorectal carcinoma	DIS5PYL0	Strong	Altered Expression	[4]
Colorectal neoplasm	DISR1UCN	Strong	Genetic Variation	[4]
Fanconi anemia complementation group O	DIS8VX8C	Strong	Autosomal recessive	[5]
Head and neck cancer	DISBPSQZ	Strong	Genetic Variation	[6]
Head and neck carcinoma	DISOU1DS	Strong	Genetic Variation	[6]
Head-neck squamous cell carcinoma	DISF7P24	Strong	Genetic Variation	[7]
Lobar holoprosencephaly	DISVK1YW	Strong	Biomarker	[3]
Neoplasm	DISZKGEW	Strong	Genetic Variation	[8]
Testicular germ cell tumor	DIS5RN24	Strong	Genetic Variation	[9]
Acute monocytic leukemia	DIS28NEL	moderate	Biomarker	[10]
Acute myelogenous leukaemia	DISCSPTN	moderate	Biomarker	[10]
Carcinoid tumor	DISMNRDC	moderate	Genetic Variation	[11]
Carcinoma	DISH9F1N	moderate	Posttranslational Modification	[12]
Myelodysplastic syndrome	DISYHNUI	moderate	Biomarker	[10]
Pancytopenia	DISVKEHV	moderate	Biomarker	[10]
Small-cell lung cancer	DISK3LZD	moderate	Genetic Variation	[11]
Fanconi's anemia	DISGW6Q8	Supportive	Autosomal recessive	[13]
Hereditary breast ovarian cancer syndrome	DISWDUGU	Supportive	Autosomal dominant	[1]
Hereditary breast carcinoma	DISAEZT5	Disputed	Autosomal dominant	[14]
Hereditary neoplastic syndrome	DISGXLG5	Disputed	CausalMutation	[15]
Chromosomal disorder	DISM5BB5	Limited	Biomarker	[16]
Fanconi anemia complementation group A	DIS8PZLI	Limited	Biomarker	[17]
Hereditary nonpolyposis colon cancer	DISPA49R	Limited	Genetic Variation	[18]
Lynch syndrome	DIS3IW5F	Limited	Genetic Variation	[18]

This DOT Affected the Drug Response of 2 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Mitomycin	DMH0ZJE	Approved	DNA repair protein RAD51 homolog 3 (RAD51C) increases the response to substance of Mitomycin.	[5]
Camptothecin	DM6CHNJ	Phase 3	DNA repair protein RAD51 homolog 3 (RAD51C) increases the response to substance of Camptothecin.	[5]

26 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 DNA repair protein RAD51 homolog 3 (RAD51C).	[19]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of DNA repair protein RAD51 homolog 3 (RAD51C).	[20]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of DNA repair protein RAD51 homolog 3 (RAD51C).	[21]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of DNA repair protein RAD51 homolog 3 (RAD51C).	[22]
Doxorubicin	DMVP5YE	Approved	Doxorubicin increases the expression of DNA repair protein RAD51 homolog 3 (RAD51C).	[23]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of DNA repair protein RAD51 homolog 3 (RAD51C).	[24]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of DNA repair protein RAD51 homolog 3 (RAD51C).	[25]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of DNA repair protein RAD51 homolog 3 (RAD51C).	[26]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of DNA repair protein RAD51 homolog 3 (RAD51C).	[27]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide affects the expression of DNA repair protein RAD51 homolog 3 (RAD51C).	[28]
Calcitriol	DM8ZVJ7	Approved	Calcitriol decreases the expression of DNA repair protein RAD51 homolog 3 (RAD51C).	[29]
Vorinostat	DMWMPD4	Approved	Vorinostat increases the expression of DNA repair protein RAD51 homolog 3 (RAD51C).	[30]
Testosterone	DM7HUNW	Approved	Testosterone decreases the expression of DNA repair protein RAD51 homolog 3 (RAD51C).	[29]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of DNA repair protein RAD51 homolog 3 (RAD51C).	[31]
Troglitazone	DM3VFPD	Approved	Troglitazone decreases the expression of DNA repair protein RAD51 homolog 3 (RAD51C).	[32]
Colchicine	DM2POTE	Approved	Colchicine decreases the expression of DNA repair protein RAD51 homolog 3 (RAD51C).	[25]
Hydroxyurea	DMOQVU9	Approved	Hydroxyurea increases the expression of DNA repair protein RAD51 homolog 3 (RAD51C).	[28]
Adenine	DMZLHKJ	Approved	Adenine decreases the expression of DNA repair protein RAD51 homolog 3 (RAD51C).	[25]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of DNA repair protein RAD51 homolog 3 (RAD51C).	[33]
Genistein	DM0JETC	Phase 2/3	Genistein increases the expression of DNA repair protein RAD51 homolog 3 (RAD51C).	[26]
phorbol 12-myristate 13-acetate	DMJWD62	Phase 2	phorbol 12-myristate 13-acetate increases the expression of DNA repair protein RAD51 homolog 3 (RAD51C).	[34]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of DNA repair protein RAD51 homolog 3 (RAD51C).	[35]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of DNA repair protein RAD51 homolog 3 (RAD51C).	[26]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of DNA repair protein RAD51 homolog 3 (RAD51C).	[36]
Coumestrol	DM40TBU	Investigative	Coumestrol increases the expression of DNA repair protein RAD51 homolog 3 (RAD51C).	[37]
Taurine	DMVW7N3	Investigative	Taurine increases the expression of DNA repair protein RAD51 homolog 3 (RAD51C).	[38]

References

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