General Information of the m6A Target Gene (ID: M6ATAR00551)
Target Name Poly [ADP-ribose] polymerase 1 (PARP1)
Synonyms
PARP-1; ADP-ribosyltransferase diphtheria toxin-like 1; ARTD1; DNA ADP-ribosyltransferase PARP1; NAD(+) ADP-ribosyltransferase 1; ADPRT 1; Poly[ADP-ribose] synthase 1; Protein poly-ADP-ribosyltransferase PARP1
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Gene Name PARP1
Chromosomal Location 1q42.12
Family ARTD/PARP family
Function
Poly-ADP-ribosyltransferase that mediates poly-ADP-ribosylation of proteins and plays a key role in DNA repair. Mediates glutamate, aspartate, serine or tyrosine ADP-ribosylation of proteins: the ADP-D-ribosyl group of NAD(+) is transferred to the acceptor carboxyl group of target residues and further ADP-ribosyl groups are transferred to the 2'-position of the terminal adenosine moiety, building up a polymer with an average chain length of 20-30 units . Serine ADP-ribosylation of proteins constitutes the primary form of ADP-ribosylation of proteins in response to DNA damage. Mainly mediates glutamate and aspartate ADP-ribosylation of target proteins in absence of HPF1. Following interaction with HPF1, catalyzes serine ADP-ribosylation of target proteins; HPF1 conferring serine specificity by completing the PARP1 active site . Also catalyzes tyrosine ADP-ribosylation of target proteins following interaction with HPF1. PARP1 initiates the repair of DNA breaks: recognizes and binds DNA breaks within chromatin and recruits HPF1, licensing serine ADP-ribosylation of target proteins, such as histones, thereby promoting decompaction of chromatin and the recruitment of repair factors leading to the reparation of DNA strand breaks . In addition to base excision repair (BER) pathway, also involved in double-strand breaks (DSBs) repair: together with TIMELESS, accumulates at DNA damage sites and promotes homologous recombination repair by mediating poly-ADP-ribosylation. Mediates the poly(ADP-ribosyl)ation of a number of proteins, including itself, APLF and CHFR. In addition to proteins, also able to ADP-ribosylate DNA: catalyzes ADP-ribosylation of DNA strand break termini containing terminal phosphates and a 2'-OH group in single- and double-stranded DNA, respectively. Required for PARP9 and DTX3L recruitment to DNA damage sites . PARP1-dependent PARP9-DTX3L-mediated ubiquitination promotes the rapid and specific recruitment of 53BP1/TP53BP1, UIMC1/RAP80, and BRCA1 to DNA damage sites. Acts as a regulator of transcription: positively regulates the transcription of MTUS1 and negatively regulates the transcription of MTUS2/TIP150. Plays a role in the positive regulation of IFNG transcription in T-helper 1 cells as part of an IFNG promoter-binding complex with TXK and EEF1A1. Involved in the synthesis of ATP in the nucleus, together with NMNAT1, PARG and NUDT5. Nuclear ATP generation is required for extensive chromatin remodeling events that are energy-consuming.
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Gene ID 142
Uniprot ID
PARP1_HUMAN
HGNC ID
HGNC:270
Ensembl Gene ID
ENSG00000143799
KEGG ID
hsa:142
Full List of m6A Methylation Regulator of This Target Gene and Corresponding Disease/Drug Response(s)
PARP1 can be regulated by the following regulator(s), and cause disease/drug response(s). You can browse detail information of regulator(s) or disease/drug response(s).
Browse Regulator
Browse Disease
Browse Drug
Methyltransferase-like 3 (METTL3) [WRITER]
Representative RNA-seq result indicating the expression of this target gene regulated by METTL3
Cell Line MOLM-13 cell line Homo sapiens
Treatment: shMETTL3 MOLM13 cells
Control: MOLM13 cells
GSE98623
Regulation
logFC: 1.69E+00
p-value: 1.05E-54
More Results Click to View More RNA-seq Results
In total 1 item(s) under this regulator
Experiment 1 Reporting the m6A Methylation Regulator of This Target Gene [1]
Response Summary m6A methyltransferase METTL3 facilitates oxaliplatin resistance in CD133+ gastric cancer stem cells by Promoting Poly [ADP-ribose] polymerase 1 (PARP1) mRNA stability which increases base excision repair pathway activity. METTTL3 enhances the stability of PARP1 by recruiting YTHDF1 to target the 3'-untranslated Region (3'-UTR) of PARP1 mRNA.
Target Regulation Up regulation
Responsed Disease Gastric cancer ICD-11: 2B72
Responsed Drug Oxaliplatin Approved
Pathway Response Nucleotide excision repair hsa03420
Signaling pathways regulating pluripotency of stem cells hsa04550
Cell Process RNA stability
Excision repair
In-vitro Model SNU-719 Gastric tubular adenocarcinoma Homo sapiens CVCL_5086
MKN74 Gastric tubular adenocarcinoma Homo sapiens CVCL_2791
HEK293T Normal Homo sapiens CVCL_0063
AGS Gastric adenocarcinoma Homo sapiens CVCL_0139
In-vivo Model 100,000 pLKO and PARP1-sh1 (PT1 and PT2) cells were mixed with matrix gel and inoculate into BALB/C nude mice, respectively. After 25 days, 6 organoid transplanted tumor mice were treated with oxaliplatin (Sellekchem, s1224) twice a week for 4 weeks at a dose of 5 mg/kg.
YTH domain-containing family protein 1 (YTHDF1) [READER]
Representative RIP-seq result supporting the interaction between PARP1 and the regulator
Cell Line Hela Homo sapiens
Regulation logFC: 1.06E+00 GSE63591
In total 1 item(s) under this regulator
Experiment 1 Reporting the m6A Methylation Regulator of This Target Gene [1]
Response Summary m6A methyltransferase METTL3 facilitates oxaliplatin resistance in CD133+ gastric cancer stem cells by Promoting PARP1 mRNA stability which increases base excision repair pathway activity. METTTL3 enhances the stability of PARP1 by recruiting Poly [ADP-ribose] polymerase 1 (PARP1) to target the 3'-untranslated Region (3'-UTR) of PARP1 mRNA.
Target Regulation Up regulation
Responsed Disease Gastric cancer ICD-11: 2B72
Responsed Drug Oxaliplatin Approved
Pathway Response Nucleotide excision repair hsa03420
Signaling pathways regulating pluripotency of stem cells hsa04550
Cell Process RNA stability
Excision repair
In-vitro Model SNU-719 Gastric tubular adenocarcinoma Homo sapiens CVCL_5086
MKN74 Gastric tubular adenocarcinoma Homo sapiens CVCL_2791
HEK293T Normal Homo sapiens CVCL_0063
AGS Gastric adenocarcinoma Homo sapiens CVCL_0139
In-vivo Model 100,000 pLKO and PARP1-sh1 (PT1 and PT2) cells were mixed with matrix gel and inoculate into BALB/C nude mice, respectively. After 25 days, 6 organoid transplanted tumor mice were treated with oxaliplatin (Sellekchem, s1224) twice a week for 4 weeks at a dose of 5 mg/kg.
Fat mass and obesity-associated protein (FTO) [ERASER]
In total 1 item(s) under this regulator
Experiment 1 Reporting the m6A Methylation Regulator of This Target Gene [2]
Response Summary Targeting FTO significantly suppresses cancer cell growth and enhances chemotherapy sensitivity, which not only mediating the balance of intracellular ROS by regulating G6PD expression, but also maintaining genome instability by regulating Poly [ADP-ribose] polymerase 1 (PARP1) expression. These findings shed light on new molecular mechanisms of CRC development and treatments mediated by m6A modification.
Target Regulation Up regulation
Responsed Disease Colorectal cancer ICD-11: 2B91
Pathway Response Glutathione metabolism hsa00480
In-vitro Model LoVo Colon adenocarcinoma Homo sapiens CVCL_0399
HCT 116 Colon carcinoma Homo sapiens CVCL_0291
HCT 8 Colon adenocarcinoma Homo sapiens CVCL_2478
SW620 Colon adenocarcinoma Homo sapiens CVCL_0547
In-vivo Model For CDX model, nude mice (female, 4-6-week-old) were subcutaneously injected with 5 × 106 HCT116 cells on the both flank. For PDX model, the patient tumors were divided into small pieces and then inoculated on both flank of nude mice. For knockdown FTO mice model, FTO mice model, two weeks after inoculation, the shFTO#3 lenti-virus injected into the tumor for three consecutive days. For combined medication mice model, intraperitoneal injection of Rhein and Olaparib was started one week after inoculation
Gastric cancer [ICD-11: 2B72]
In total 2 item(s) under this disease
Experiment 1 Reporting the m6A-centered Disease Response [1]
Response Summary m6A methyltransferase METTL3 facilitates oxaliplatin resistance in CD133+ gastric cancer stem cells by Promoting Poly [ADP-ribose] polymerase 1 (PARP1) mRNA stability which increases base excision repair pathway activity. METTTL3 enhances the stability of PARP1 by recruiting YTHDF1 to target the 3'-untranslated Region (3'-UTR) of PARP1 mRNA.
Responsed Disease Gastric cancer [ICD-11: 2B72]
Target Regulator Methyltransferase-like 3 (METTL3) WRITER
Target Regulation Up regulation
Responsed Drug Oxaliplatin Approved
Pathway Response Nucleotide excision repair hsa03420
Signaling pathways regulating pluripotency of stem cells hsa04550
Cell Process RNA stability
Excision repair
In-vitro Model SNU-719 Gastric tubular adenocarcinoma Homo sapiens CVCL_5086
MKN74 Gastric tubular adenocarcinoma Homo sapiens CVCL_2791
HEK293T Normal Homo sapiens CVCL_0063
AGS Gastric adenocarcinoma Homo sapiens CVCL_0139
In-vivo Model 100,000 pLKO and PARP1-sh1 (PT1 and PT2) cells were mixed with matrix gel and inoculate into BALB/C nude mice, respectively. After 25 days, 6 organoid transplanted tumor mice were treated with oxaliplatin (Sellekchem, s1224) twice a week for 4 weeks at a dose of 5 mg/kg.
Experiment 2 Reporting the m6A-centered Disease Response [1]
Response Summary m6A methyltransferase METTL3 facilitates oxaliplatin resistance in CD133+ gastric cancer stem cells by Promoting PARP1 mRNA stability which increases base excision repair pathway activity. METTTL3 enhances the stability of PARP1 by recruiting Poly [ADP-ribose] polymerase 1 (PARP1) to target the 3'-untranslated Region (3'-UTR) of PARP1 mRNA.
Responsed Disease Gastric cancer [ICD-11: 2B72]
Target Regulator YTH domain-containing family protein 1 (YTHDF1) READER
Target Regulation Up regulation
Responsed Drug Oxaliplatin Approved
Pathway Response Nucleotide excision repair hsa03420
Signaling pathways regulating pluripotency of stem cells hsa04550
Cell Process RNA stability
Excision repair
In-vitro Model SNU-719 Gastric tubular adenocarcinoma Homo sapiens CVCL_5086
MKN74 Gastric tubular adenocarcinoma Homo sapiens CVCL_2791
HEK293T Normal Homo sapiens CVCL_0063
AGS Gastric adenocarcinoma Homo sapiens CVCL_0139
In-vivo Model 100,000 pLKO and PARP1-sh1 (PT1 and PT2) cells were mixed with matrix gel and inoculate into BALB/C nude mice, respectively. After 25 days, 6 organoid transplanted tumor mice were treated with oxaliplatin (Sellekchem, s1224) twice a week for 4 weeks at a dose of 5 mg/kg.
Colorectal cancer [ICD-11: 2B91]
In total 1 item(s) under this disease
Experiment 1 Reporting the m6A-centered Disease Response [2]
Response Summary Targeting FTO significantly suppresses cancer cell growth and enhances chemotherapy sensitivity, which not only mediating the balance of intracellular ROS by regulating G6PD expression, but also maintaining genome instability by regulating Poly [ADP-ribose] polymerase 1 (PARP1) expression. These findings shed light on new molecular mechanisms of CRC development and treatments mediated by m6A modification.
Responsed Disease Colorectal cancer [ICD-11: 2B91]
Target Regulator Fat mass and obesity-associated protein (FTO) ERASER
Target Regulation Up regulation
Pathway Response Glutathione metabolism hsa00480
In-vitro Model LoVo Colon adenocarcinoma Homo sapiens CVCL_0399
HCT 116 Colon carcinoma Homo sapiens CVCL_0291
HCT 8 Colon adenocarcinoma Homo sapiens CVCL_2478
SW620 Colon adenocarcinoma Homo sapiens CVCL_0547
In-vivo Model For CDX model, nude mice (female, 4-6-week-old) were subcutaneously injected with 5 × 106 HCT116 cells on the both flank. For PDX model, the patient tumors were divided into small pieces and then inoculated on both flank of nude mice. For knockdown FTO mice model, FTO mice model, two weeks after inoculation, the shFTO#3 lenti-virus injected into the tumor for three consecutive days. For combined medication mice model, intraperitoneal injection of Rhein and Olaparib was started one week after inoculation
Oxaliplatin [Approved]
In total 2 item(s) under this drug
Experiment 1 Reporting the m6A-centered Drug Response [1]
Response Summary m6A methyltransferase METTL3 facilitates oxaliplatin resistance in CD133+ gastric cancer stem cells by Promoting Poly [ADP-ribose] polymerase 1 (PARP1) mRNA stability which increases base excision repair pathway activity. METTTL3 enhances the stability of PARP1 by recruiting YTHDF1 to target the 3'-untranslated Region (3'-UTR) of PARP1 mRNA.
Target Regulator Methyltransferase-like 3 (METTL3) WRITER
Target Regulation Up regulation
Responsed Disease Gastric cancer ICD-11: 2B72
Pathway Response Nucleotide excision repair hsa03420
Signaling pathways regulating pluripotency of stem cells hsa04550
Cell Process RNA stability
Excision repair
In-vitro Model SNU-719 Gastric tubular adenocarcinoma Homo sapiens CVCL_5086
MKN74 Gastric tubular adenocarcinoma Homo sapiens CVCL_2791
HEK293T Normal Homo sapiens CVCL_0063
AGS Gastric adenocarcinoma Homo sapiens CVCL_0139
In-vivo Model 100,000 pLKO and PARP1-sh1 (PT1 and PT2) cells were mixed with matrix gel and inoculate into BALB/C nude mice, respectively. After 25 days, 6 organoid transplanted tumor mice were treated with oxaliplatin (Sellekchem, s1224) twice a week for 4 weeks at a dose of 5 mg/kg.
Experiment 2 Reporting the m6A-centered Drug Response [1]
Response Summary m6A methyltransferase METTL3 facilitates oxaliplatin resistance in CD133+ gastric cancer stem cells by Promoting PARP1 mRNA stability which increases base excision repair pathway activity. METTTL3 enhances the stability of PARP1 by recruiting Poly [ADP-ribose] polymerase 1 (PARP1) to target the 3'-untranslated Region (3'-UTR) of PARP1 mRNA.
Target Regulator YTH domain-containing family protein 1 (YTHDF1) READER
Target Regulation Up regulation
Responsed Disease Gastric cancer ICD-11: 2B72
Pathway Response Nucleotide excision repair hsa03420
Signaling pathways regulating pluripotency of stem cells hsa04550
Cell Process RNA stability
Excision repair
In-vitro Model SNU-719 Gastric tubular adenocarcinoma Homo sapiens CVCL_5086
MKN74 Gastric tubular adenocarcinoma Homo sapiens CVCL_2791
HEK293T Normal Homo sapiens CVCL_0063
AGS Gastric adenocarcinoma Homo sapiens CVCL_0139
In-vivo Model 100,000 pLKO and PARP1-sh1 (PT1 and PT2) cells were mixed with matrix gel and inoculate into BALB/C nude mice, respectively. After 25 days, 6 organoid transplanted tumor mice were treated with oxaliplatin (Sellekchem, s1224) twice a week for 4 weeks at a dose of 5 mg/kg.
References
Ref 1 METTL3 promotes oxaliplatin resistance of gastric cancer CD133+?stem cells by promoting PARP1 mRNA stability. Cell Mol Life Sci. 2022 Feb 18;79(3):135. doi: 10.1007/s00018-022-04129-0.
Ref 2 FTO promotes colorectal cancer progression and chemotherapy resistance via demethylating G6PD/PARP1. Clin Transl Med. 2022 Mar;12(3):e772. doi: 10.1002/ctm2.772.