title: Repair of O-alkylpyrimidines in mammalian cells: a present consensus.
abstract: Enzymatic repair of the O-alkylpyrimidines (O2- and O4-alkylthymine, O2-alkylcytosine) and alkyl phosphotriesters has been studied in Escherichia coli, and the two proteins involved, a glycosylase (DNA-3-methyladenine glycosylase) and a methyltransferase (DNA-O6-methylguanine:protein-L-cysteine S-methyltransferase, EC 2.1.1.63), have been well characterized. In mammals or mammalian cells treated with carcinogenic alkylating agents, loss of these derivatives has been demonstrated repeatedly. Nevertheless, mammalian repair proteins that are analogous to those from E. coli do not detectably act on these alkyl derivatives. A variety of techniques has been used by many investigators in the United States and Europe, who conclude here that the mode of O-alkylpyrimidine and alkyl phosphotriester repair in mammalian cells differs from that in E. coli. New approaches and methods are needed to characterize these processes at the biochemical and molecular level.
authors.affiliation: St. Jude Children's Research Hospital, Memphis, TN 38101.
authors.forename: T P
authors.initials: TP
authors.lastname: Brent
authors.forename: M E
authors.initials: ME
authors.lastname: Dolan
authors.forename: H
authors.initials: H
authors.lastname: Fraenkel-Conrat
authors.forename: J
authors.initials: J
authors.lastname: Hall
authors.forename: P
authors.initials: P
authors.lastname: Karran
authors.forename: L
authors.initials: L
authors.lastname: Laval
authors.forename: G P
authors.initials: GP
authors.lastname: Margison
authors.forename: R
authors.initials: R
authors.lastname: Montesano
authors.forename: A E
authors.initials: AE
authors.lastname: Pegg
authors.forename: P M
authors.initials: PM
authors.lastname: Potter
mesh_terms: D000477:Alkylating Agents / Q000494:pharmacology; D000478:Alkylation; D000818:Animals; D002478:Cells, Cultured; D045647:DNA Glycosylases; D004260:DNA Repair; D008322:Mammals; D008780:Methyltransferases / Q000378:metabolism; D009699:N-Glycosyl Hydrolases / Q000378:metabolism; D019853:O(6)-Methylguanine-DNA Methyltransferase; D011743:Pyrimidines / Q000378:metabolism*; D051381:Rats
chemical_list: D000477:Alkylating Agents; D011743:Pyrimidines; D008780:Methyltransferases; D019853:O(6)-Methylguanine-DNA Methyltransferase; C021565:3-methyladenine-DNA glycosylase; D045647:DNA Glycosylases; D009699:N-Glycosyl Hydrolases