ran1+ controls the transition from mitotic division to meiosis in fission yeast.

We have investigated the genetic and physiological control of meiosis in fission yeast. Nutritionally depleted h+/h- diploid cells become irreversibly commited to meiosis immediately prior to the initiation of premeiotic S phase. Premeiotic DNA synthesis requires matP+, matM+, mei2+ and mei3+ but not the mitotic cell cycle control gene, cdc2+. ran1+ is an essential gene, loss of which provokes sexual conjugation, premeiotic DNA synthesis, pseudo-meiosis and the sporulation of haploid cells. Our experiments suggest that sexual differentiation is achieved physiologically by the inhibition of ran1+ activity in a two-step process. In the first step, partial inhibition of ran1+ in starved haploid cells, leads to cell cycle arrest in G1 followed by sexual conjugation. In the second step, a pathway requiring the matP+, matM+ and mei3+ genes of the newly-formed zygote, further inhibits ran1+ and thereby commits the cell to meiosis. mei2+ is required for meiotic commitment after full inhibition of ran1+. ran1+ is normally essential for vegetative cell reproduction but is inessential in cells which have abnormally high levels of cAMP-dependent protein kinase. We propose that the ran1+ gene encodes a highly controlled protein kinase which shares key substrates with cAMP-dependent protein kinase.