Cyclin-dependent kinases are critical for eukaryotic cell cycle control. In budding yeast, 9 different cyclins all activate the same cyclin- dependent kinase Cdc28, resulting in diverse biological responses depending on the cyclin complexed to Cdc28. Little is known about the basis for cyclin specificity of action. The G1 cyclins of budding yeast, CLN1, CLN2 and CLN3, are required for the Start transition at the beginning of the cell cycle, and act by binding to and activation the Cdc28 cyclin-dependent kinase catalytic subunit. Although the yeast G1 cyclins are functionally redundant, they nevertheless differ in their biological mode of action. This system may provide a model for cyclin specificity of action in eukaryotic in eukaryotic cell cycle control. This question is significant for human health because of the involvement of multiple human G1 cyclins in controlling cell proliferation. This proposal comprises direct examination of the contrasting effects of different cyclins on subcellular localization of the cyclin-Cdk complex, and analysis of a highly cyclin-specific biological response, the regulation of the mating factor response pathway by the G1 cyclin Cln2.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM047238-07
Application #
6329729
Study Section
Genetics Study Section (GEN)
Program Officer
Zatz, Marion M
Project Start
1993-05-01
Project End
2002-11-30
Budget Start
2000-12-01
Budget End
2001-11-30
Support Year
7
Fiscal Year
2001
Total Cost
$258,590
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
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
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
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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