Ung1p-mediated uracil-base excision repair in mitochondria is responsible for the petite formation in thymidylate deficient yeast.
The budding yeast CDC21 gene, which encodes thymidylate synthase, is crucial in the thymidylate biosynthetic pathway. Early studies revealed that high frequency of petites were formed in heat-sensitive cdc21 mutants grown at the permissive temperature. However, the molecular mechanism involved in such petite formation is largely unknown. Here we used a yeast cdc21-1 mutant to demonstrate that the mutant cells accumulated dUMP in the mitochondrial genome. When UNG1 (encoding uracil-DNA glycosylase) was deleted from cdc21-1, we found that the ung1Delta cdc21-1 double mutant reduced frequency of petite formation to the level found in wild-type cells. We propose that the initiation of Ung1p-mediated base excision repair in the uracil-laden mitochondrial genome in a cdc21-1 mutant is responsible for the mitochondrial petite mutations.
Institute of Biochemistry and Molecular Biology, National Yang-Ming University, Taipei, Taiwan.
Chia-Yi
CY
Chien
Chen-Kung
CK
Chou
Jin-Yuan
JY
Su
D004260:DNA Repair / Q000502:physiology*; D004271:DNA, Fungal / Q000378:metabolism; D004272:DNA, Mitochondrial / Q000235:genetics / Q000378:metabolism*; D005434:Flow Cytometry; D016196:S Phase; D012441:Saccharomyces cerevisiae / Q000201:enzymology / Q000235:genetics / Q000378:metabolism*; D013938:Thymidine Monophosphate / Q000378:metabolism*; D014498:Uracil / Q000378:metabolism*; D051981:Uracil-DNA Glycosidase / Q000378:metabolism / Q000502:physiology*
D004271:DNA, Fungal; D004272:DNA, Mitochondrial; D013938:Thymidine Monophosphate; D014498:Uracil; D051981:Uracil-DNA Glycosidase