Phylogenetic evidence of a role for 5-hydroxymethyluracil-DNA glycosylase in the maintenance of 5-methylcytosine in DNA.

5-Hydroxymethyluracil (HmUra) is formed in DNA as a product of oxidative attack on the methyl group of thymine. It is also the product of the deamination of 5-hydroxymethylcytosine (HmCyt) which may be formed via oxidation of 5-methylcytosine (MeCyt). HmUra is removed from DNA by a DNA glycosylase which, together with HmCyt-DNA glycosylase, is unique among DNA repair enzymes in being present in mammalian cells but absent from bacteria and yeast. We found HmUra-DNA glycosylase activity in a wide variety of vertebrate and invertebrate animals (except Drosophila) and in protozoans. In most vertebrate organisms the highest specific activity was in nervous and immune system tissue. The phylogenetic distribution of HmUra-DNA glycosylase correlates with the presence of 5-methylcytosine (MeCyt) as a regulator of gene expression. This distribution of activity supports the contention that HmUra-DNA glycosylase aids in the maintenance of methylated sites in DNA.