title: N4-methylation of cytosine drastically favors the formation of (6-4) photoproducts in a TCG context.
abstract: Methylation of cytosine is a common biological process both in prokaryotic and eukaryotic cells. In addition to 5-methylcytosine (5mC), some bacterial species contain in their genome N(4) -methylcytosine (N4mC). Methylation at C5 has been shown to enhance the formation of pyrimidine dimeric photoproducts but nothing is known of the effect of N4 methylation on UV-induced DNA damage. In the present work, we compared the yield and the nature of bipyrimidine photoproducts induced in a series of trinucleotides exhibiting a TXG sequence where X is either T, C, 5mC or N4mC. HPLC associated to tandem mass spectrometry was used to quantify cyclobutane pyrimidine dimers (CPD), (6-4) photoproducts (64PP) and their Dewar valence isomer. Methylation at position N4 was found to drastically increase the reactivity of C upon exposure to both UVC and UVB and to favor the formation of 64PP. In contrast methylation at C5 increased the yield of CPD at the expense of 64PP. In addition, enhancement of photoreactivity by C5 methylation was much higher in the UVB than in the UVC range. These results show the drastic effect of the methylation site on the photochemistry of cytosine.
authors.affiliation: University Grenoble Alpes, INAC-LCIB, LAN, Grenoble, France; CEA, INAC-SCIB, LAN, Grenoble, France.
authors.forename: Thierry
authors.initials: T
authors.lastname: Douki
authors.forename: Jarah A
authors.initials: JA
authors.lastname: Meador
authors.forename: Izabel
authors.initials: I
authors.lastname: Bérard
authors.forename: Aude
authors.initials: A
authors.lastname: Wack
mesh_terms: D002851:Chromatography, High Pressure Liquid; D003596:Cytosine / Q000378:metabolism*; D019281:Dimerization; D008745:Methylation; D011740:Pyrimidine Dimers / Q000378:metabolism*; D053719:Tandem Mass Spectrometry
chemical_list: D011740:Pyrimidine Dimers; D003596:Cytosine