Hhal and Hpall DNA methyltransferases bind DNA mismatches, methylate uracil and block DNA repair

Allen S. Yang, Jiang cheng Shen, Jean marc Zingg, Sha Mi, Peter A. Jones

Research output: Contribution to journalArticlepeer-review

127 Scopus citations

Abstract

The hydrolytic deamination of 5-methyicytosine (5-mC) to thymine (T) is believed to be responsible for the high mutability of the CpG dinucleotide in DNA. We have shown a possible alternate mechanism for mutagenesis at CpG in which Hpall DNA-(cytosine-5) methyltransferase (M.Hpall) can enzymatically deaminate cytosine (C) to uracil (U) in DNA [Shen,J.-C., Rideout,W.M., III and Jones,P.A., Cell, 71, 1073-1080, (1992)]. Both the hydrolytic deamination of 5-mC and enzymatic deamination of C create premutagenic DNA mismatches (G:U and G:T) with the guanine (G) originally paired to the normal C. Surprisingly, we found that DNA-(cytosine-5) methyltransferases have higher affinities for these DNA mismatches than for their normal G:C targets and are capable of transfer ring a methyl group to the 5-position of U, creating T at low efficiencies. This binding by methyltransferase to mismatches at the recognition site prevented repair of G:U mismatches by uracil DNA glycosyiase in vitro.

Original languageEnglish (US)
Pages (from-to)1380-1387
Number of pages8
JournalNucleic acids research
Volume23
Issue number8
DOIs
StatePublished - Apr 25 1995
Externally publishedYes

ASJC Scopus subject areas

  • Genetics

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