SPECIFICITY OF CYCLIN FUNCTION AT CELL CYCLE INITIATION

Rockefeller University, New York NY

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Abstract

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.