Uracil Accumulation and Mutagenesis Dominated by Cytosine Deamination in CpG Dinucleotides in Mice Lacking UNG and SMUG1.

ABSTRACT: Both a DNA lesion and an intermediate for antibody maturation, uracil is primarily processed by base excision repair (BER), either initiated by uracil-DNA glycosylase (UNG) or by single-strand selective monofunctional uracil DNA glycosylase (SMUG1). The relative in vivo contributions of each glycosylase remain elusive. To assess the impact of SMUG1 deficiency, we measured uracil and 5-hydroxymethyluracil, another SMUG1 substrate, in Smug1 ^-/- mice. We found that 5-hydroxymethyluracil accumulated in Smug1 ^-/- tissues and correlated with 5-hydroxymethylcytosine levels. The highest increase was found in brain, which contained about 26-fold higher genomic 5-hydroxymethyluracil levels than the wild type. Smug1 ^-/- mice did not accumulate uracil in their genome a

SUBMITTER: Alsoe L 

PROVIDER: S-EPMC5543110 | biostudies-literature | 2017 Aug

REPOSITORIES: biostudies-literature