Recovery of the Yeast Cell Cycle from Heat Shock-induced G1 Arrest Involves a Positive Regulation of G1Cyclin Expression by the S Phase Cyclin Clb5

Abstract

In the yeast Saccharomyces cerevisiae, heat shock stress induces a variety of cellular responses including a transient cell cycle arrest before G(1)/S transition. Previous studies have suggested that this G(1) delay is probably attributable to a reduced level of the G(1) cyclin gene (CLN1 and CLN2) transcripts. Here we report our finding that the G(1) cyclin Cln3 and the S cyclin Clb5 are the key factors required for recovery from heat shock-induced G(1) arrest. Heat shock treatment of G(1) cells lacking either CLN3 or CLB5/CLB6 functions leads to prolonged cell cycle arrest before the initiation of DNA synthesis, concomitant with a severe deficiency in bud formation. The inability of the clb5 clb6 mutant to resume normal budding after heat shock treatment is unanticipated, since the S phase cyclins are generally thought to be required mainly for initiation of DNA synthesis and have no significant roles in bud formation in the presence of functional G(1) cyclins. Further studies reveal that the accumulation of G(1) cyclin transcripts is markedly delayed in the clb5 clb6 mutant following heat shock treatment, indicating that the CLN gene expression may require Clb5/Clb6 to attain a threshold level for driving the cell cycle through G(1)/S transition. Consistent with this assumption, overproduction of Clb5 greatly enhances the transcription of at least two G(1) cyclin genes (CLN1 and CLN2) in heat-shocked G(1) cells. These results suggest that Clb5 may positively regulate the expression of G(1) cyclins during cellular recovery from heat shock-induced G(1) arrest. Additional evidence is presented to support a role for Clb5 in maintaining the synchrony between budding and DNA synthesis during normal cell division as well.