INCREASE IN DATP POOL IN APHIDICOLIN-RESISTANT MUTANTS OF MOUSE FM3A CELLS

Mutants that were resistant to aphidicolin were isolated from mutagenized mouse FM3A cells at a frequency of about 10-6. Resistance to aphidicolin in these mutants was not due to an effect on [3H]thymidine incorporation into DNA, DNA synthesis in permeabilized cells, or DNA polymerase α. All the mutants showed a greatly increased dATP pool and decreased ability to incorporate [3H]deoxycytidine into DNA. They also showed cross-resistance to both 1-β-D-arabinofuranosyladenine and 1-β-D-arabinofuranosylcytosine. These results indicate that an enzyme involved in production of dATP or its regulation is altered in these mutants. It is suggested that dATP competes with aphidocolin at its killing site or that dATP reverses the effect of aphidicolin by some unknown mechanism in vivo. © 1979.