Disease relevance of CPD-1094

• Orf135 from Escherichia coli Is a Nudix hydrolase specific for CTP, dCTP, and 5-methyl-dCTP [1].
• 5-methyl-dCTP deaminase induced by bacteriophage XP-12 [2].

High impact information on CPD-1094

• Orf135 from Escherichia coli is a new member of the Nudix (nucleoside diphosphate linked to some other moiety, x) hydrolase family of enzymes with substrate specificity for CTP, dCTP, and 5-methyl-dCTP [1].
• During subsequent rounds of replication, the injected 5-methyl dCTP became depleted but methylation at CpG sites was still elevated presumably due to the action of a methyltransferase enzyme [3].
• Direct induction of DNA hypermethylation in sea urchin embryos by microinjection of 5-methyl dCTP stimulates early histone gene expression and leads to developmental arrest [3].
• Interestingly, the development of embryos injected with 5-methyl dCTP typically was arrested at the blastula stage, and analysis of the genomic DNA extracted from injected embryos showed a significant increase in the endogenous methylation content [3].
• Activation of the maternally preset program of apoptosis by microinjection of 5-aza-2'-deoxycytidine and 5-methyl-2'-deoxycytidine-5'-triphosphate in Xenopus laevis embryos [4].

Biological context of CPD-1094

• Because of the nature of its substrate specificity, Orf135 may play a role in pyrimidine biosynthesis, lipid biosynthesis, and in controlling levels of 5-methyl-dCTP in the cell [1].
• These results show that 5-Aza-CdR and 5-methyl-dCTP are incorporated into DNA and induce apoptosis, probably through alteration of DNA methylation coupled with inhibition of DNA replication and/or transcription [4].
• The present study examines the effects on embryogenesis of microinjecting Xenopus laevis fertilized eggs with 5-aza-2'-deoxycytidine (5-Aza-CdR), which induces hypomethylation of DNA, and 5-methyl-2'- deoxycytidine-5'-triphosphate (5-methyl-dCTP), which induces hypermethylation of DNA [4].
• Gene silencing in mammalian cells by uptake of 5-methyl deoxycytidine-5'-triphosphate [5].

Analytical, diagnostic and therapeutic context of CPD-1094

• PCR with 5-methyl-dCTP replacing dCTP [6].

References