Roles of the RAM signaling network in cell cycle progression in Saccharomyces cerevisiae.

The Saccharomyces cerevisiae Hym1p, Mob2p, Tao3p, Cbk1p, Sog2p and Kic1p proteins are thought to function together in the RAM signaling network, which controls polarized growth, cell separation and cell integrity. Whether these proteins also function as a network to affect cell proliferation is not clear. Here we examined cells lacking or over-expressing RAM components, and evaluated the timing of initiation of DNA replication in each case. Our results suggest opposing roles of RAM proteins, where only Hym1p can promote the transition from the G1 to S phase of the cell cycle. We also uncovered additive growth defects in strains lacking several pair-wise combinations of RAM proteins, possibly arguing for multiple roles of RAM components in the overall control of cell proliferation. Finally, our findings suggest that Hym1p requires the Dcr2p phosphatase to promote the G1/S transition, but it does not require the G1 cyclin Cln3p or the RAS pathway. Taken together, our results point to a complex regulation of cell proliferation by RAM proteins, in a non-uniform manner that was not previously anticipated.