title: Antifolate response in replication arrest mutants of Saccharomyces cerevisiae.
abstract: OBJECTIVE
  Thymidine deprivation is a common cancer treatment. This study examines the role of replication arrest and uracil DNA repair in response to thymidine deprivation.
  
  
  METHODS
  Strains of S. cerevisiae deficient in various replication and DNA repair functions were tested for sensitivity to thymidine deprivation induced by the antifolate aminopterin. Cell survival and DNA content were assayed following drug treatment.
  
  
  RESULTS
  Most arrest mutants were more sensitive to aminopterin than was the parental strain. Inactivation of uracil glycosylase in arrest mutants led to a partial reduction in toxicity for some double-mutants. DNA content during exposure to aminopterin was similar in parental and single mutants. However, cells deficient in both arrest and uracil glycosylase functions exhibited continued DNA synthesis, suggesting that uracil glycosylase activity contributes to replication arrest during thymidine deprivation.
  
  
  CONCLUSIONS
  Replication arrest and uracil DNA repair are important and overlapping determinants of cellular response to thymidine deprivation.
authors: University of Minnesota Medical School, Duluth Campus, Duluth, MN, 55805, USA. Kenneth.dornfeld@essentiahealth.org
authors: Ken
authors: K
authors: Dornfeld
mesh_terms: D000630:Aminopterin / Q000494:pharmacology*; D004260:DNA Repair / Q000187:drug effects*; D004261:DNA Replication / Q000187:drug effects*; D005493:Folic Acid Antagonists / Q000494:pharmacology*; D009154:Mutation / Q000235:genetics; D012441:Saccharomyces cerevisiae / Q000187:drug effects* / Q000235:genetics / Q000254:growth & development; D015996:Survival Rate; D013936:Thymidine / Q000378:metabolism*; D051981:Uracil-DNA Glycosidase / Q000378:metabolism
chemical_list: D005493:Folic Acid Antagonists; D051981:Uracil-DNA Glycosidase; D000630:Aminopterin; D013936:Thymidine
keywords: Saccharomyces cerevisiae; Thymidine deprivation; replication stress; uracil glycosylase