Bất hoạt và methyl hóa retrovirus xảy ra ngay sau khi giới thiệu vào các tế bào phôi (Jahner et al 1982; Stewart et al 1982), nhưng methyl hóa cũng có thể được tiếp theo với một sự kiện im lặng ban đầu phiên mã, vì những thay đổi trong thay đổi histone có thể được phát hiện trước khi methyl hóa gen vừa được giới thiệu | CTMI 2006 301 259-281 Springer-Verlag Berlin Heidelberg 2006 Mutagenesis at MethylatedCpGSequences G. p. Pfeifer Division a Research institute of the City ofHope Duarte CA 91010 USA gpfeifer@ 1 2 The p53 Gene as a Mutation 3 Deamination of 4 Enzymatic Deaminadon Reacuions . 268 5 Methylated npG Seqeoncesaa nreferred Targets for Mutagens ann Carcinogens .269 Abstract SaMeOoy-oySosine in DNA is genetically unstable. Mediated CpG rnCpG sequences icoquo-aly undergo mutation resulting in a geneoal depletion of this dinucleotide sequence in mammalian genomes. In human genetic disease- and cancerrelevant genesmCpG sequences are matronal is tn almost univerc sally accepteddogma that qa. mutct onsasc caused by random deamentSscn cf 5-methylcytosines. However it is plausible that mCpG transitions are not caused simply by spontantousdtaminvtirn ot 5-mtOinlty0oeSnc indoubl SsandeO DNA Out by other oroanoot e- e ofo-g esamplt mCnG-doeiUtc nattmodlficanioo n_ueo-dogenouspotxegeiesus moSaaum ot aStereaidvsSyi bereoovecryfoctsru operatrng at mCpG sepuences eub nbumotingdoamsnatiuf. WotSee oq-co-bd-n mCpGseuntntes are favored tcsgtls foc spetOicoddnenofc mutaoe aodearsentoens. wteocnjaomt to anotheepytttmdmel5-mttUdlcotosiyeortaerentiblly tndsrgoto s qhr-indoccn pyrimidine dimer formation. Certain polycyclic aromatic hydrocarbons form guanine adducts ancmducet to T teelloveostou mutetione nttd high soiaoStvitybtmCpG sequences. 1 Introduction About 3 -4 of all cytosines in mammalian DNA are converted to 5-mefhylcytosinepafter DNA replication through an enzymatic process involv- 260 G. p. Pfeifer ing DNAmeAyltransferases. Most or 1 of these 5-methylcytosine bases are found in the dinucleotide sequence CpG Riggs and Jones 1983 . As discussed in this chapter and elsewhere in this book CpG methylation may play a critical role hr and sequence-selective .
