A classic way to isolate thymidylate synthase–negative mutants of bacteriais to treat a growing culture with thymidine and trimethoprim. Most ofthe cells are killed, and the survivors are greatly enriched in thymidylatesynthase–negative mutants.(a) What phenotype would allow you to identify these mutants?(b) What is the biochemical rationale for the selection? (That is, why are themutants not killed under these conditions?)(c) How would the procedure need to be modified to select mammalian cellmutants defective in thymidylate synthase?

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Chapter10: From Proteins To Phenotypes
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A classic way to isolate thymidylate synthase–negative mutants of bacteria
is to treat a growing culture with thymidine and trimethoprim. Most of
the cells are killed, and the survivors are greatly enriched in thymidylate
synthase–negative mutants.
(a) What phenotype would allow you to identify these mutants?
(b) What is the biochemical rationale for the selection? (That is, why are the
mutants not killed under these conditions?)
(c) How would the procedure need to be modified to select mammalian cell
mutants defective in thymidylate synthase?

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