The synthesis of 2'-deoxycytidine triphosphate carrying mercaptoethyl groups at position 4 of cytosine is described. This nucleoside triphosphate was reacted with a maleimido-peptide carrying the c-myc tag-sequence to yield a peptide-nucleoside triphosphate chimera. Primer extension studies showed that the nucleoside triphosphate modified with the peptide sequence is incorporated by DNA polymerases opposite guanine.
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http://dx.doi.org/10.1080/15257770008045445 | DOI Listing |
J Biol Chem
December 2024
Virus and Cellular Stress Unit, Department of Virology, Université Paris Cité, Institut Pasteur, 28 rue du Dr. Roux, F-75724 Paris cedex 15, France. Electronic address:
Perturbation of the deoxyribonucleotide triphosphate (dNTP) pool is recognized for contributing to the mutagenic processes involved in oncogenesis. The RAS gene family encodes well characterized oncoproteins whose structure and function are among the most frequently altered in several cancers. In this work, we show that fluctuation of the dNTP pool induces CG->TA mutations across the whole genome, including RAS gene at codons for glycine 12 and 13, known hotspots in cancers.
View Article and Find Full Text PDFImmunology
December 2024
Department of Molecular and Medical Pharmacology, UCLA, Los Angeles, California, USA.
Autoreactive, aberrantly activated lymphocytes that target myelin antigens in the central nervous system (CNS) are primary drivers of the autoimmune disease multiple sclerosis (MS). Proliferating cells including activated lymphocytes require deoxyribonucleoside triphosphates (dNTPs) for DNA replication. dNTPs can be synthesised via the de novo pathway from precursors such as glucose and amino acids or the deoxyribonucleoside salvage pathway from extracellular deoxyribonucleosides.
View Article and Find Full Text PDFAnal Bioanal Chem
December 2024
Department of Biomedical and Clinical Sciences, Linköping University, Linköping, Sweden.
In the treatment of diseases such as acute childhood leukaemia (ALL) and inflammatory bowel disease (IBD), the thiopurines azathioprine, 6-mercaptopurine, and 6-thioguanine are used. Thiopurines are antimetabolites and immunomodulators used to maintain remission in patients. They are all prodrugs and must be converted into the competing antimetabolites thioguanosine triphosphate and deoxythioguanosine triphosphate for final incorporation into RNA or DNA.
View Article and Find Full Text PDFCell Death Dis
October 2024
Department of Hepatobiliary Surgery and Fujian Institute of Hepatobiliary Surgery, Fujian Medical University Union Hospital, Fuzhou, China.
Nucleosides Nucleotides Nucleic Acids
October 2024
Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan.
Damaged 2'-deoxyribonucleotides cause mutations, cancer, cell death, and aging. The Orf135 (NudG) protein catalyzes the hydrolysis of various 2'-deoxyribonucleotides including an oxidized form of dATP, 2-oxo-1,2-dihydro-2'-deoxyadenosine 5'-triphosphate (dATP, 2-hydroxy-2'-deoxyadenosine 5'-triphosphate). The best substrate is 5-methyl-2'-deoxycytidine 5'-triphosphate (dCTP), and the protein prefers dCTP over dATP by ∼200-fold in vitro.
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