m6A Target Gene Information

General Information of the m6A Target Gene (ID: M6ATAR00483)
Target Name Mismatch repair endonuclease PMS2 (PMS2)
Synonyms
DNA mismatch repair protein PMS2; PMS1 protein homolog 2; PMSL2
    Click to Show/Hide
Gene Name PMS2
Family DNA mismatch repair MutL/HexB family. {ECO:0000305}.
Function
Component of the post-replicative DNA mismatch repair system (MMR). Heterodimerizes with MLH1 to form MutL alpha. DNA repair is initiated by MutS alpha (MSH2-MSH6) or MutS beta (MSH2-MSH3) binding to a dsDNA mismatch, then MutL alpha is recruited to the heteroduplex. Assembly of the MutL-MutS-heteroduplex ternary complex in presence of RFC and PCNA is sufficient to activate endonuclease activity of PMS2. It introduces single-strand breaks near the mismatch and thus generates new entry points for the exonuclease EXO1 to degrade the strand containing the mismatch. DNA methylation would prevent cleavage and therefore assure that only the newly mutated DNA strand is going to be corrected. MutL alpha (MLH1-PMS2) interacts physically with the clamp loader subunits of DNA polymerase III, suggesting that it may play a role to recruit the DNA polymerase III to the site of the MMR. Also implicated in DNA damage signaling, a process which induces cell cycle arrest and can lead to apoptosis in case of major DNA damages. {ECO:0000269|PubMed:16873062, ECO:0000269|PubMed:18206974, ECO:0000269|PubMed:23709753}.
    Click to Show/Hide
Gene ID 5395
Uniprot ID
PMS2_HUMAN
HGNC ID
HGNC:9122
Ensembl Gene ID
ENSG00000122512
KEGG ID
hsa:5395
Full List of m6A Methylation Regulator of This Target Gene and Corresponding Disease/Drug Response(s)
PMS2 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
Methyltransferase-like 5 (METTL5) [WRITER]
 Regulator Info 
In total 1 item(s) under this regulator
Experiment 1 Reporting the m6A Methylation Regulator of This Target Gene [1]
Response Summary knocking down METTL5 could significantly activate apoptosis and inhibit endometrial carcinoma(EC) development via MMR administration.METTL5 expression in UCEC tumor tissue was increased, and UCEC patients with high METTL5 expression had worse prognostic outcomes. METTL5 knockdown induced the MSH2, MSH6 and Mismatch repair endonuclease PMS2 (PMS2) expression in MMR.
Target Regulation Up regulation
Responsed Disease Endometrial cancer ICD-11: 2C76
 Disease Info 
Pathway Response Mismatch repair hsa03430
Cell Process DNA mismatch repair
Microsatellite instability
In-vitro Model CP-H058 (Normal endometrial cells)
KLE Endometrial adenocarcinoma Homo sapiens CVCL_1329
RL95-2 Endometrial adenosquamous carcinoma Homo sapiens CVCL_0505
Ishikawa Endometrial adenocarcinoma Homo sapiens CVCL_2529
ECC-1 Endometrial Cancer Homo sapiens CVCL_7260
In-vivo Model The male BALB/c nude mice were randomized divide into two groups, each group including six 4 weeks old nude mice. Investigators were blinded to the treatment groups during data collection and subsequent data analysis. In the subcutaneous xenograft model, 5 × 105 cells were subcutaneously injected in the right flanks of nude mice. In the orthotopic intracranial mouse model, each mouse was intracranially injected with 1 × 105 luciferase transfected U87MG cells in 10 uL PBS solution.
Endometrial cancer [ICD-11: 2C76]
 Disease Info 
In total 1 item(s) under this disease
Experiment 1 Reporting the m6A-centered Disease Response [1]
Response Summary knocking down METTL5 could significantly activate apoptosis and inhibit endometrial carcinoma(EC) development via MMR administration.METTL5 expression in UCEC tumor tissue was increased, and UCEC patients with high METTL5 expression had worse prognostic outcomes. METTL5 knockdown induced the MSH2, MSH6 and Mismatch repair endonuclease PMS2 (PMS2) expression in MMR.
Responsed Disease Endometrial cancer [ICD-11: 2C76]
Target Regulator Methyltransferase-like 5 (METTL5) WRITER
 Regulator Info 
Target Regulation Up regulation
Pathway Response Mismatch repair hsa03430
Cell Process DNA mismatch repair
Microsatellite instability
In-vitro Model CP-H058 (Normal endometrial cells)
KLE Endometrial adenocarcinoma Homo sapiens CVCL_1329
RL95-2 Endometrial adenosquamous carcinoma Homo sapiens CVCL_0505
Ishikawa Endometrial adenocarcinoma Homo sapiens CVCL_2529
ECC-1 Endometrial Cancer Homo sapiens CVCL_7260
In-vivo Model The male BALB/c nude mice were randomized divide into two groups, each group including six 4 weeks old nude mice. Investigators were blinded to the treatment groups during data collection and subsequent data analysis. In the subcutaneous xenograft model, 5 × 105 cells were subcutaneously injected in the right flanks of nude mice. In the orthotopic intracranial mouse model, each mouse was intracranially injected with 1 × 105 luciferase transfected U87MG cells in 10 uL PBS solution.
References
Ref 1 The potential role of methyltransferase-like 5 in deficient mismatch repair of uterine corpus endometrial carcinoma. Bioengineered. 2022 Mar;13(3):5525-5536. doi: 10.1080/21655979.2022.2036912.