Cloning of caf1(+), caf2(+) and caf4(+) from Schizosaccharomyces pombe: their involvement in multidrug resistance, UV and pH sensitivity

We previously identified four nuclear genes (caf1(+) to caf4(+)) in Schizos accharomyces pombe, mutations in which can confer caffeine resistance. Here we report the cloning and sequencing of caf1(+), caf2(+) and caf4(+). All three genes are allelic to genes (hba1(+), crm1(+) and trr1(+), respectivel y) involved in multidrug resistance mechanisms or in stress response system s. In agreement with this the caffeine-resistant mutants caf1 (hba1)-21, ca f2 (crm1)-3 and caf4 (trr1)-83 are also resistant to brefeldin. Disruption of caf1 (hba1)(+) and caf4 (trr1)(+) makes cells sensitive to high pH. The overlapping ranges of pleiotropic effects and the genetic interaction detec ted between caf1 (hbal)(+) and caf2 (crm1)(+) suggest that the three genes function in interlinked systems.