A NEW CLASS OF URACIL-DNA GLYCOSYLASES RELATED TO HUMAN THYMINE-DNA GLYCOSYLASE

MISPAIRS in DNA of guanine with uracil and thymine can arise as a resu lt of deamination of cytosine and 5-methylcytosine, respectively. In h umans such mispairs are removed by thymine-DNA glycosylase (TDG)(1-3). By deleting the carboxy and amino termini of this enzyme we have iden tified a core region capable of processing G/U but not G/T mispairs. W e have further identified two bacterial proteins with strong sequence homology to this core and shown that the homologue from Escherichia co li (dsUDG) can remove uracil from G/U mispairs. This enzyme is likely to act as a back-up to the highly efficient and abundant enzyme uracil -DNA glycosylase (UDG) which is found in most organisms. Pupating inse cts have been reported to lack UDG activity(4), but we have identified an enzyme similar to dsUDG in cell lines from three different insect species. These data imply the existence of a family of double-strand-s pecific uracil-DNA glycosylases which, although they are subservient t o UDG in mast organisms, may constitute the first line of defence agai nst the mutagenic effects of cytosine deamination in insects.