The fission yeast rDNA-binding protein Reb1 regulates G1 phase under nutritional stress.
Yeast Reb1 and its mammalian ortholog TTF1 are conserved Myb-type DNA-binding proteins that bind to specific sites near the 3'-end of rRNA genes (rDNA). Here, they participate in the termination of transcription driven by RNA polymerase I and block DNA replication forks approaching in the opposite direction. We found that Schizosaccharomyces pombe Reb1 also upregulates 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 or cyclosome ('APC/C') in G1, targeting B-cyclin for proteasomal 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 with this new role for Reb1 in the regulation of the G1-S transition, reb1Δ and wee1(ts) mutations are synthetically lethal owing to the inability of these cells to lengthen G1 before entering S phase. Similarly, reb1Δ cdc10(ts) cells are unable to arrest in G1 and die at the semi-permissive temperature.
Department of Cell Proliferation and Development, Centro de Investigaciones Biológicas, Consejo Superior de Investigaciones Científicas, Ramiro de Maeztu 9, 28040 Madrid, Spain.
Leonor
L
Rodríguez-Sánchez
María
M
Rodríguez-López
Zaira
Z
García
María
M
Tenorio-Gómez
Jorge B
JB
Schvartzman
Dora B
DB
Krimer
Pablo
P
Hernández
D001483:Base Sequence; D004275:DNA, Ribosomal / Q000235:genetics / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D016193:G1 Phase; D015966:Gene Expression Regulation, Fungal; D008969:Molecular Sequence Data; D009584:Nitrogen / Q000172:deficiency; D011485:Protein Binding; D012568:Schizosaccharomyces / Q000166:cytology / Q000235:genetics / Q000254:growth & development / Q000502:physiology*; D029702:Schizosaccharomyces pombe Proteins / Q000235:genetics / Q000378:metabolism*; D013312:Stress, Physiological; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*
D004275:DNA, Ribosomal; D004268:DNA-Binding Proteins; D029702:Schizosaccharomyces pombe Proteins; D014157:Transcription Factors; C512907:reb1 protein, S pombe; D009584:Nitrogen