Open AccessEfficient removal of uracil from G.U mispairs by themismatch-specific thymine DNA glycosylase from HeLa cells.
Author(s) -
Petra Neddermann,
Josef Jiricny
Publication year - 1994
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.011
H-Index - 771
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.91.5.1642
Subject(s) - deamination , uracil , dna glycosylase , guanine , thymine , cytosine , dna , biochemistry , uracil dna glycosylase , chemistry , pyrimidine , biology , dna repair , microbiology and biotechnology , enzyme , nucleotide , gene
The uracil DNA glycosylases (EC 3.2.2.3)characterized to date remove uracil from DNA irrespective of whether it is basepaired with adenine or mispaired with guanine in double-stranded substrates orwhether it is found in single-stranded DNA. We report here the characterizationof uracil glycosylase activity that can remove the base solely from a mispairwith guanine. It does not recognize uracil either in A.U pairs or insingle-stranded substrates. The enzyme, a 55-kDa polypeptide, was previouslycharacterized as a mismatch-specific thymine DNA glycosylase and was thought tobe responsible solely for the correction (to G.C) of G.T mispairs that arise asa result of spontaneous hydrolytic deamination of 5-methylcytosine to thymine.Given the broader substrate specificity of the enzyme (in addition to uracil andthymine, the protein can also remove 5-bromouracil from mispairs with guanine),we propose that its biological role in vivo may also include the correction of asubset of G.U mispairs inefficiently removed by the more abundant ubiquitousuracil glycosylases, such as those arising from cytosine deamination in G+C-richregions of the genome.