The focus of our work is the regulation of the G1/S transition in the budding yeast, S. cerevisiae. Previous work in several labs, including ours, has established the CLN1, CLN2, and CLN3 genes of yeast as critical in regulation of this transition, both by external factors (hormones, nutrients) and internal factors (cell size). The homology of these genes with cyclins, and their genetic and biochemical interactions with the product of the cdc2 homolog in this organism, CDC28, combined with the apparent specificity of their action to the G1/S transition (as opposed to the G2/M transition for previously described cyclins) suggests the idea that the CLN proteins may be 'G1 cyclins'. Since the G1/S transition is a primary point of regulation in many organisms, including humans, and since the regulation of this transition is grossly abnormal in cancer, it is important to determine the mechanism of action and regulation of CLN genes, as well as to determine the universality through evolution of the system. These are the issues addressed in this application.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM047238-02
Application #
2184628
Study Section
Genetics Study Section (GEN)
Project Start
1993-05-01
Project End
1997-04-30
Budget Start
1994-05-01
Budget End
1995-04-30
Support Year
2
Fiscal Year
1994
Total Cost
Indirect Cost
Name
Rockefeller University
Department
Genetics
Type
Other Domestic Higher Education
DUNS #
071037113
City
New York
State
NY
Country
United States
Zip Code
10065
Li, Yinyin; Cross, Frederick R; Chait, Brian T (2014) Method for identifying phosphorylated substrates of specific cyclin/cyclin-dependent kinase complexes. Proc Natl Acad Sci U S A 111:11323-8
Cross, Frederick R; Pecani, Kresti (2011) Efficient and rapid exact gene replacement without selection. Yeast 28:167-79
Rosenberg, Jessica S; Cross, Frederick R; Funabiki, Hironori (2011) KNL1/Spc105 recruits PP1 to silence the spindle assembly checkpoint. Curr Biol 21:942-7
Cross, Frederick R; Buchler, Nicolas E; Skotheim, Jan M (2011) Evolution of networks and sequences in eukaryotic cell cycle control. Philos Trans R Soc Lond B Biol Sci 366:3532-44
Oikonomou, Catherine; Cross, Frederick R (2011) Rising cyclin-CDK levels order cell cycle events. PLoS One 6:e20788
Oikonomou, Catherine; Cross, Frederick R (2010) Frequency control of cell cycle oscillators. Curr Opin Genet Dev 20:605-12
Robbins, Jonathan A; Cross, Frederick R (2010) Requirements and reasons for effective inhibition of the anaphase promoting complex activator CDH1. Mol Biol Cell 21:914-25
Lu, Ying; Cross, Frederick R (2010) Periodic cyclin-Cdk activity entrains an autonomous Cdc14 release oscillator. Cell 141:268-79
Wäsch, R; Robbins, J A; Cross, F R (2010) The emerging role of APC/CCdh1 in controlling differentiation, genomic stability and tumor suppression. Oncogene 29:1-10
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

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