Dividing cells must co-ordinate their rate of division with their rate of cell growth and protein synthesis. In S. cerevisiae, the G1 cyclin C1n3 is central to this co-ordination. Cells use the amount and rate of synthesis of C1n3 to measure readiness for cell division. When cells achieve """"""""critical size,"""""""" C1n3 activates the transcription factors SBF and MBF, which in turn induce the transcription of over 200 genes. These 200 genes are directly responsible for cell cycle progress into S-phase. It is not understood how small changes in C1n3 abundance or concentration at """"""""critical size"""""""" are translated into activation of SBFand MBF-dependent genes, and this is the issue addressed in this proposal. Experiments in Aim 1 will discover the molecular connection between Cln3 and the transcription factors SBF and MBF. Experiments in Aim 2 will characterize the changes that occur at SBF-dependent promoters as a consequence of C1n3 activity. Experiments in Aim 3 will characterize several proteins that interact genetically or physically with Cln3, and which may help environmental and physiological events signal to C1n3, or may help C1n3 signal to its target transcription factors.

National Institute of Health (NIH)
National Institute of General Medical Sciences (NIGMS)
Research Project (R01)
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Cell Development and Function Integrated Review Group (CDF)
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Zatz, Marion M
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State University New York Stony Brook
Schools of Medicine
Stony Brook
United States
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Gao, Shujuan; Honey, Sangeet; Futcher, Bruce et al. (2016) The non-homologous end-joining pathway of S. cerevisiae works effectively in G1-phase cells, and religates cognate ends correctly and non-randomly. DNA Repair (Amst) 42:1-10
Zhao, Gang; Chen, Yuping; Carey, Lucas et al. (2016) Cyclin-Dependent Kinase Co-Ordinates Carbohydrate Metabolism and Cell Cycle in S. cerevisiae. Mol Cell 62:546-57
Garg, Angad; Futcher, Bruce; Leatherwood, Janet (2015) A new transcription factor for mitosis: in Schizosaccharomyces pombe, the RFX transcription factor Sak1 works with forkhead factors to regulate mitotic expression. Nucleic Acids Res 43:6874-88
Cai, Ying; Futcher, Bruce (2013) Effects of the yeast RNA-binding protein Whi3 on the half-life and abundance of CLN3 mRNA and other targets. PLoS One 8:e84630
Ferrezuelo, Francisco; Colomina, Neus; Futcher, Bruce et al. (2010) The transcriptional network activated by Cln3 cyclin at the G1-to-S transition of the yeast cell cycle. Genome Biol 11:R67
Di Talia, Stefano; Wang, Hongyin; Skotheim, Jan M et al. (2009) Daughter-specific transcription factors regulate cell size control in budding yeast. PLoS Biol 7:e1000221
Wang, Hongyin; Carey, Lucas B; Cai, Ying et al. (2009) Recruitment of Cln3 cyclin to promoters controls cell cycle entry via histone deacetylase and other targets. PLoS Biol 7:e1000189
Honey, Sangeet; Futcher, Bruce (2007) Roles of the CDK phosphorylation sites of yeast Cdc6 in chromatin binding and rereplication. Mol Biol Cell 18:1324-36
Jorgensen, Paul; Edgington, Nicholas P; Schneider, Brandt L et al. (2007) The size of the nucleus increases as yeast cells grow. Mol Biol Cell 18:3523-32
Futcher, Bruce (2006) Metabolic cycle, cell cycle, and the finishing kick to Start. Genome Biol 7:107

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