A cytosine methyltransferase converts 5-methylcytosine in DNA to thymine
- PMID: 7578083
- DOI: 10.1021/bi00045a016
A cytosine methyltransferase converts 5-methylcytosine in DNA to thymine
Abstract
Sites of cytosine methylation are known to be hot spots for C.G to T.A mutations in a number of systems, including human cells. Traditionally, spontaneous hydrolytic deamination of 5-methylcytosine to thymine has been invoked as the cause of this phenomenon. We show here that a bacterial cytosine methyltransferase can convert 5-methylcytosine in DNA to thymine and that this reaction creates a mutational hot spot at a site of DNA methylation. The reaction is fairly insensitive to the methyl donor in the reaction, S-adenosylmethionine. In many cancers, the most frequent class of mutations is C to T changes within CG dinucleotides of the tumor suppressor gene p53. Because of the similarities of the reaction mechanisms of mammalian and bacterial enzymes and the physiology of the cancer cells, this reaction is expected to contribute to mutations at CG dinucleotides in precancerous cells.
Similar articles
-
Cytosine deaminations catalyzed by DNA cytosine methyltransferases are unlikely to be the major cause of mutational hot spots at sites of cytosine methylation in Escherichia coli.Proc Natl Acad Sci U S A. 1994 Feb 15;91(4):1574-8. doi: 10.1073/pnas.91.4.1574. Proc Natl Acad Sci U S A. 1994. PMID: 8108447 Free PMC article.
-
Lowering S-adenosylmethionine levels in Escherichia coli modulates C-to-T transition mutations.J Bacteriol. 2001 Feb;183(3):921-7. doi: 10.1128/JB.183.3.921-927.2001. J Bacteriol. 2001. PMID: 11208790 Free PMC article.
-
High frequency mutagenesis by a DNA methyltransferase.Cell. 1992 Dec 24;71(7):1073-80. doi: 10.1016/s0092-8674(05)80057-1. Cell. 1992. PMID: 1473145
-
Principal causes of hot spots for cytosine to thymine mutations at sites of cytosine methylation in growing cells. A model, its experimental support and implications.Mutat Res. 1999 Jul;437(1):11-20. doi: 10.1016/s1383-5742(99)00065-4. Mutat Res. 1999. PMID: 10425387 Review.
-
DNA methylation and mutation.Mutat Res. 1993 Jan;285(1):61-7. doi: 10.1016/0027-5107(93)90052-h. Mutat Res. 1993. PMID: 7678134 Review.
Cited by
-
An overview of chemical processes that damage cellular DNA: spontaneous hydrolysis, alkylation, and reactions with radicals.Chem Res Toxicol. 2009 Nov;22(11):1747-60. doi: 10.1021/tx900242k. Chem Res Toxicol. 2009. PMID: 19757819 Free PMC article. Review.
-
Repeat-Induced Point Mutation and Other Genome Defense Mechanisms in Fungi.Microbiol Spectr. 2017 Jul;5(4):10.1128/microbiolspec.funk-0042-2017. doi: 10.1128/microbiolspec.FUNK-0042-2017. Microbiol Spectr. 2017. PMID: 28721856 Free PMC article. Review.
-
Identification of transcriptome SNPs for assessing allele-specific gene expression in a super-hybrid rice Xieyou9308.PLoS One. 2013 Apr 17;8(4):e60668. doi: 10.1371/journal.pone.0060668. Print 2013. PLoS One. 2013. PMID: 23613738 Free PMC article.
-
Nonsense mutations in the hairless gene underlie APL in five families of Pakistani origin.J Dermatol Sci. 2007 Dec;48(3):207-11. doi: 10.1016/j.jdermsci.2007.07.007. Epub 2007 Sep 14. J Dermatol Sci. 2007. PMID: 17869066 Free PMC article.
-
Synthesis and properties of oligonucleotides containing 5-formyl-2'-deoxycytidine: in vitro DNA polymerase reactions on DNA templates containing 5-formyl-2'-deoxycytidine.Nucleic Acids Res. 2001 Jun 15;29(12):2456-63. doi: 10.1093/nar/29.12.2456. Nucleic Acids Res. 2001. PMID: 11410651 Free PMC article.
Publication types
MeSH terms
Substances
Grants and funding
LinkOut - more resources
Other Literature Sources
Molecular Biology Databases
Research Materials
Miscellaneous