Fission yeast rDNA-binding protein Reb1 regulates G1 phase under nutritional stress

Abstract

Yeast Reb1 and its mammalian ortholog TTF1 are conserved Myb-type DNAbinding proteins that bind to specific sites near the 3’-end of rRNA genes (rDNA). Here, they participate in the termination of RNA polymerase I-driven transcription and block DNA replication forks approaching in the opposite direction. We found that Schizosaccharomyces pombe Reb1 also up-regulates transcription of the ste9+ gene that is required for nitrogen starvation-induced growth arrest with a G1 DNA content and sexual differentiation. Ste9 activates the anaphase-promoting complex/cyclosome (APC/C) in G1 targeting B-cyclin for proteasome degradation in response to nutritional stress. Reb1 binds in vivo and in vitro to a specific DNA sequence at the promoter of ste9+, similar to the sequence recognized in the rDNA, and this binding is required for ste9+ transcriptional activation and G1 arrest. This suggests that Reb1 acts as a link between rDNA metabolism and cell cycle control in response to nutritional stress. In agreement to this new role of Reb1 in the regulation of G1/S transition, reb1Δ and wee1ts mutations are synthetically lethal due to the deficiency of these cells to lengthen G1 before entering S phase. Similarly,reb1Δ cdc10ts cells are unable to arrest in G1 and die at the semi-permissive temperature.