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uracil DNA glycosylase, spontaneous mutation, base excision repair, Schizosaccharomyces pombe
Uracil in DNA arises by spontaneous deamination of cytosine to generate U:G mispair, which leads to C:G to T:A mutations. Usually this DNA damage is repaired by base excision repair initiated by removal of uracil through uracil DNA glycosylase (UDG). Schizosaccharomyces pombe has two kinds of UDG proteins, Ung1p and Thp1p, which belong to the UDG superfamily with evolutionally conserved protein folding. To clarify the roles of these UDGs in vivo, we constructed UDG-deficient cells by disruption of ung1 and thp1 genes. Spontaneous mutation frequencies of ung1 and thp1 single mutants were significantly higher than that of the wild-type cells. Concurrent inactivation of ung1 and thp1 further increased the mutation frequency, indicating that Ung1p and Thp1p appear to function in an additive mode. Exogenous expression of Ung1p and Thp1p complemented the mutator phenotype of UDG-deficient cells. Moreover, expression of Ung1p or Thp1p in the ung1/thp1 double mutant partially suppressed spontaneous mutagenesis. These results indicated that both UDG proteins synergistically play important roles in avoidance from mutagenesis caused by spontaneous deamination.
Research papers (academic journals)
