DNA and RNA Pyrimidine Nucleobase Alkylation at the Carbon-5 Position.
The carbon 5 of pyrimidine nucleobases is a privileged position in terms of nucleoside modification in both DNA and RNA. The simplest modification of uridine at this position is methylation leading to thymine. Thymine is an integral part of the standard nucleobase repertoire of DNA that is synthesized at the nucleotide level. However, it also occurs in RNA, where it is synthesized posttranscriptionally at the polynucleotide level. The cytidine analogue 5-methylcytidine also occurs in both DNA and RNA, but is introduced at the polynucleotide level in both cases. The same applies to a plethora of additional derivatives found in nature, resulting either from a direct modification of the 5-position by electrophiles or by further derivatization of the 5-methylpyrimidines. Here, we review the structural diversity of these modified bases, the variety of cofactors that serve as carbon donors, and the common principles shared by enzymatic mechanisms generating them.
IMoPA UMR7365 CNRS-UL, BioPole de l'Université de Lorraine, 9 avenue de la Foret de Haye, 54505, Vandoeuvre-les-Nancy, France. motorine5@univ-lorraine.fr.
Yuri
Y
Motorin
Department of Biochemistry, University of Cape Coast, College of Agriculture and Natural Sciences, School of Biological Sciences, Cape Coast, Ghana.|Institute of Pharmacy and Biochemistry, Johannes Gutenberg University Mainz, Staudingerweg 5, 55128, Mainz, Germany.
Salifu
S
Seidu-Larry
Institute of Pharmacy and Biochemistry, Johannes Gutenberg University Mainz, Staudingerweg 5, 55128, Mainz, Germany. mhelm@uni-mainz.de.
Mark
M
Helm
D000478:Alkylation / Q000235:genetics; D002244:Carbon / Q000737:chemistry; D003562:Cytidine / Q000031:analogs & derivatives / Q000737:chemistry / Q000235:genetics; D004247:DNA / Q000737:chemistry* / Q000235:genetics; D019175:DNA Methylation / Q000235:genetics*; D015394:Molecular Structure; D011741:Pyrimidine Nucleosides / Q000737:chemistry* / Q000235:genetics; D012313:RNA / Q000737:chemistry* / Q000235:genetics; D013940:Thymidylate Synthase / Q000737:chemistry / Q000235:genetics; D014529:Uridine / Q000737:chemistry / Q000235:genetics
D011741:Pyrimidine Nucleosides; D003562:Cytidine; D012313:RNA; D002244:Carbon; D004247:DNA; D013940:Thymidylate Synthase; C016568:5-methylcytidine; D014529:Uridine