RAN1 + controls the transition from mitotic division to meiosis in fission yeast

Abstract

Summary 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.