aidB is one of the four genes of E. coli that is induced by alkylating agents and regulated by Ada protein. Three genes (ada, alkA, and alkB) encode DNA repair proteins that remove or repair alkylated bases. However, the role of AidB remains unclear despite extensive efforts to determine its function in cells exposed to alkylating agents. The E. coli AidB protein was identified as a component of the protein complex that assembles at strong promoters. We demonstrate that AidB protein preferentially binds to UP elements, AT rich transcription enhancer sequences found upstream of many highly expressed genes, several DNA repair genes, and housekeeping genes. AidB allows efficient transcription from promoters containing an UP element upon exposure to a DNA methylating agent and protects downstream genes from DNA damage. The DNA binding domain is required to target AidB to specific genes preferentially protecting them from alkylation damage. However, deletion of AidB's DNA binding domain does not prevent its antimutagenic activity, instead this deletion appears to allow AidB to function as a cytoplasmic alkylation resistance protein. Our studies identify the role of AidB in alkylating agent exposed cells and suggest a new cellular strategy in which a subset of the genome is preferentially protected from damage by alkylating agents.
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http://dx.doi.org/10.1016/j.dnarep.2011.06.001 | DOI Listing |
Pharmaceuticals (Basel)
January 2025
Jeffrey Cheah School of Medicine and Health Sciences, Monash University Malaysia, Jalan Lagoon Selatan, Bandar Sunway 47500, Selangor, Malaysia.
: The multiple drug-resistant phenomenon has long since plagued the effectiveness of various chemotherapies used in the treatment of patients with glioblastoma (GBM), which is still incurable to this day. ATP-binding cassette (ABC) transporters function as drug transporters and have been touted to be the main culprits in developing resistance to xenobiotic drugs in GBM. : This review systematically analyzed the efficacy of ABC transporters against various anticancer drugs from 16 studies identified from five databases (PubMed, Medline, Embase, Scopus, and ScienceDirect).
View Article and Find Full Text PDFPharmaceuticals (Basel)
January 2025
Departamento de Farmacia, Escuela Nacional de Ciencias Biológicas, Instituto Politécnico Nacional, Av. Wilfrido Massieu 399, Mexico City C.P. 07738, Mexico.
: In recent years the global incidence of cancer during pregnancy is rising, occurring in 1 out of every 1000 pregnancies. In this regard, the most used chemotherapy drugs to treat cancer are alkylating agents such as cyclophosphamide (Cp). Despite its great efficacy, has been associated with the production of oxidative stress and DNA damage, leading to embryotoxicity, genotoxicity, and teratogenicity in the developing .
View Article and Find Full Text PDFInt J Mol Sci
January 2025
Department of Pharmaceutical Biochemistry, Poznan University of Medical Sciences, Rokietnicka 3, 60-806 Poznań, Poland.
Adult-type diffuse gliomas are characterized by inevitable recurrence and very poor prognosis. Novel treatment options, including multimodal drugs or effective drug combinations, are therefore eagerly awaited. Tinostamustine is an alkylating and histone deacetylase inhibiting molecule with great potential in cancer treatment.
View Article and Find Full Text PDFSci Rep
January 2025
Department of Hematology, the Second Affiliated Hospital of Nanjing Medical University, Nanjing, 210003, China.
It has been documented that D-dimer levels have potential utility as a measure of tumor activity in diffuse large B-cell lymphoma (DLBCL), however whether it can be used as a predictive marker of treatment outcome has not been established. This study means to retrospectively evaluate the role of D-dimer in prediction of treatment efficacy in patients with DLBCL. 151 patients with newly diagnosed DLBCL were enrolled.
View Article and Find Full Text PDFMutat Res Genet Toxicol Environ Mutagen
January 2025
Free University of Berlin, Institute of Pharmacy, Pharmacology and Toxicology, Berlin, Germany; BASF SE, Experimental Toxicology and Ecology, Ludwigshafen am Rhein, Germany.
Mutagenicity testing is a component of the hazard assessment of industrial chemicals, biocides, and pesticides. Mutations induced by test substances can be detected by in vitro and in vivo methods that have been adopted as OECD Test Guidelines. One of these in vivo methods is the Transgenic Rodent Assay (TGRA), OECD test guideline no.
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