Fission yeast int6 is not essential for global translation initiation, butdeletion of int6(+) causes hypersensitivity to caffeine and affects spore formation

Mammalian INT6 protein has been considered to be a subunit of the eukaryoti c translation initiation factor, eIF3. The Int6 locus is also known as a co mmon integration site of mouse mammary tumor virus (MMTV). However, the fun ction of Int6 in translation initiation and the mechanism of Int6-mediated tumor induction are yet to be explored. In this study, the fission yeast, S chizosaccharomyces pombe, int6(+), which is 43% identical to the mammalian counterpart, was deleted. Despite the evidence that the majority of Int6 pr otein was associated with 40S particles in this organism, strains lacking i nt6(+) (Delta int6) were viable and showed only moderate inhibition in the rate of in vivo global protein synthesis. Polysome profile analysis showed no apparent defects in translation initiation. Delta int6 exhibited a hyper sensitivity to caffeine, which could be suppressed by the addition of sorbi tol to the growth medium. This and other phenotypes would imply that int6() is required for the integrity of cell membrane. In meiosis, Delta int6 pr oduced incomplete tetrads frequently. High dosage expression of a truncated mutant of int6(+) conferred a hypersensitivity to caffeine, but did not ca use the defect in meiosis. A possible link between the function of int6(+) and the Delta int6-phenotypes is discussed.