Disease relevance of C02026

• A triplex-forming oligonucleotide (TFO) complementary to the polypurine-polypyrimidine region of the nef gene of the Human Immunodeficiency Virus (HIV) was labeled with 125I at the C5 position of a single deoxycytosine residue [1].
• Deoxycytosine methylation within CpG islands of tumor suppressor genes plays a prominent role in the development and progression of drug-resistant ovarian cancer [2].

High impact information on C02026

• Somatic hypermutation and class-switch-recombination are initiated by the deamination of deoxycytosine in DNA by activation-induced-deaminase, AID [3].
• The results reveal that deoxyguanine and complementary deoxycytosine residues are preferential binding sites of trans-[Pt(NH3)2Cl2] in the interstrand adducts [4].
• Substitution at the C-5 position of cytosine by alkyl groups (ethyl and methyl) markedly enhanced the dCTPalphaB resistance towards exonuclease III (5-Et-dCTPalphaB >5-Me-dCTPalphaB >dCTPalphaB approximately 5-Br-dCTPalphaB >5-I-dCTPalphaB), thereby generating DNA sequences that better define the deoxycytosine positions [5].
• Inhibition was most pronounced (IC50 = 0.21 microM, standard assay) for a 5'-cholesteryl heteropolymer consisting of 15 phosphorothioate deoxynucleotides with alternating deoxycytosine and deoxyadenosine (Chol-PS-d(CA)7C) [6].
• As in other higher eukaryotes, DNA methylation in plants is predominantly found at deoxycytosine residues, while deoxyadenosine residues are not methylated at significant levels [7].

Biological context of C02026

• Methylation of deoxycytosine residues in plant nuclear DNA at CpG dinucleotides is generally assumed to suppress transcription, while deoxyadenosine methylation on recombinant reporter gene constructs transiently introduced into plant cells increases expression by uncharacterized mechanisms [8].
• 5-Aza-C, when present for the penultimate preharvest cell cycle, induced SCEs in a manner consistent with a directly measured reduction in deoxycytosine methylation in cellular DNA [9].
• In the vertebrate genome, methylation of deoxycytosine residues of CpGs dinucleotide has been associated with transcriptional silencing of genes, parental imprinting, X-inactivation and chromatin remodelling [10].
• One possible explanation for this phenomenon is that the factor IX gene (located on the X chromosome) has undergone extensive deoxycytosine methylation and subsequent spontaneous deamination mutagenesis, resulting in a net C to thymine (and G to adenine) transition [11].
• The method of calculation includes use of a molecular model of plasmid DNA duplex with bound TFO carrying a labelled 125I at position C5 of a single deoxycytosine residue, a source of Auger spectra, Monte Carlo electron track structure and the ensuing chemistry codes, to simulate the distribution of breaks produced in both strands of a plasmid DNA [12].

Associations of C02026 with other chemical compounds

• The increase in deoxycytosine methylation is so far the only detected effect of the carcinogen methapyrilene on DNA which is absent in rats treated with its non-carcinogenic analogs [13].
• Total RNA from 23 cows at various stages of development was isolated from mammary parenchyma and subjected to Northern blot analysis using human transforming growth factor-alpha 32P-labeled deoxycytosine triphosphate cDNA probe [14].
• Deoxycytosine was the only incorporated nucleotide opposite deoxyinosine during PCR amplification, irrespective of origin of DNA polymerase [15].

Gene context of C02026

• These results indicate that the HURP gene might be a potential oncogenic gene and capable of enhancing the chemosensitivity of deoxycytosine analogs in NIH3T3 cells [16].
• Conformational studies of R- and S-alpha-(N6-adenyl)styrene oxide adducts mismatched with deoxycytosine at position X6 in d(CGGACXAGAAG).d(CTTCTCGTCCG), incorporating codons 60, 61 (underlined), and 62 of the human N-ras protooncogene, are described [17].
• The exonuclease activity associated with DNA polymerase delta removes araCMP from 3' termini with the same efficiency that it removes a paired 3' deoxycytosine suggesting that the proofreading exonucleases associated with DNA polymerases might remove aranucleotides inefficiently [18].

References