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Construction of a chemiluminescent biosensor based on enzymatic extension and click chemistry for sensitive measurement of MGMT activity in human breast tissues.
Talanta
January 2025
School of Chemistry and Chemical Engineering, State Key Laboratory of Digital Medical Engineering, Southeast University, Nanjing, 211189, China. Electronic address:
O-methylguanine methyltransferase (MGMT) is responsible for dealkylation of naturally occurring O-methylguanines, and it is closely related with DNA replication, transcription, and cancers. Herein, we develop a chemiluminescent biosensor based on enzymatic extension and click chemistry for sensitive measurement of MGMT activity. When MGMT is present, the MGMT-catalyzed demethylation reaction initiates the cleavage of biotinylated dumbbell probes by PvuII restrictive enzyme, releasing two DNA fragments with 3'-OH end.
View Article and Find Full Text PDFIntegration of Demethylation-Activated DNAzyme with a Single Quantum Dot Nanosensor for Sensitive Detection of O-Methylguanine DNA Methyltransferase in Breast Tissues.
Anal Chem
March 2024
School of Chemistry and Chemical Engineering, Southeast University, Nanjing 211189, China.
O-Methylguanine-DNA-methyltransferase (MGMT) is a demethylation protein that dynamically regulates the O-methylguanine modification (O MeG), and dysregulated MGMT is implicated in various malignant tumors. Herein, we integrate demethylation-activated DNAzyme with a single quantum dot nanosensor to sensitively detect MGMT in breast tissues. The presence of MGMT induces the demethylation of the O MeG-caged DNAzyme and the restoration of catalytic activity.
View Article and Find Full Text PDFEpigenetic Activation of TUSC3 Sensitizes Glioblastoma to Temozolomide Independent of MGMT Promoter Methylation Status.
Int J Mol Sci
October 2023
Department of Neuro-Oncology, H. Lee Moffitt Cancer Center and Research Institute, 12902 Magnolia Drive, Tampa, FL 33612, USA.
Temozolomide (TMZ) is an important first-line treatment for glioblastoma (GBM), but there are limitations to TMZ response in terms of durability and dependence on the promoter methylation status of the DNA repair gene O-methylguanine DNA methyltransferase (). MGMT-promoter-hypermethylated (MGMT-M) GBMs are more sensitive to TMZ than MGMT-promoter-hypomethylated (MGMT-UM) GBMs. Moreover, TMZ resistance is inevitable even in TMZ-sensitive MGMT-M GBMs.
View Article and Find Full Text PDFArchaeal DNA alkylation repair conducted by DNA glycosylase and methyltransferase.
Appl Microbiol Biotechnol
May 2023
Marine Science & Technology Institute, College of Environmental Science and Engineering, Yangzhou University, Yangzhou City, China.
Alkylated bases in DNA created in the presence of endogenous and exogenous alkylating agents are either cytotoxic or mutagenic, or both to a cell. Currently, cells have evolved several strategies for repairing alkylated base. One strategy is a base excision repair process triggered by a specific DNA glycosylase that is used for the repair of the cytotoxic 3-methyladenine.
View Article and Find Full Text PDFAscorbate content of clinical glioma tissues is related to tumour grade and to global levels of 5-hydroxymethyl cytosine.
Sci Rep
September 2022
Mackenzie Cancer Research Group, Department of Pathology and Biomedical Science, University of Otago Christchurch, Christchurch, New Zealand.
Gliomas are incurable brain cancers with poor prognosis, with epigenetic dysregulation being a distinctive feature. 5-hydroxymethylcytosine (5-hmC), an intermediate generated in the demethylation of 5-methylcytosine, is present at reduced levels in glioma tissue compared with normal brain, and that higher levels of 5-hmC are associated with improved patient survival. DNA demethylation is enzymatically driven by the ten-eleven translocation (TET) dioxygenases that require ascorbate as an essential cofactor.
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