A CASEIN KINASE-I ISOFORM IS REQUIRED FOR PROPER CELL-CYCLE PROGRESSION IN THE FERTILIZED MOUSE OOCYTE

Casein kinase I is a family of serine/threonine protein kinases common to all eukaryotes. In yeast, casein kinase I homologues have been lin ked to the regulation of growth, DNA repair and cell division, In addi tion, their subcellular localization to membraneous structures and the nucleus is essential for function, In higher eukaryotes, there exist seven genetically distinct isoforms: alpha, beta, gamma 1, gamma 2, ga mma 3, delta and epsilon. Casein kinase I alpha exhibits a cell cycle- dependent subcellular localization including an association with cytos olic vesicular structures and the nucleus during interphase, and the s pindle during mitosis, casein kinase I has also been shown to modulate critical regulators of growth and DNA synthesis/repair in mammalian c ells such as SV40 large T antigen and p53, These results suggest that casein kinase I may be involved in processes similar to those ascribed to the yeast casein kinase I homologues. To define a role for casein kinase I alpha in cell cycle regulation, the mouse oocyte was utilized because of its well-defined cell cycle and ease of micromanipulation, Immunofluorescence studies from meiosis I of maturation to the first zygotic cleavage demonstrated that the kinase was associated with stru ctures similar to those previously reported, Microinjection of casein kinase Ice antibodies at metaphase II-arrest and G(2) phase, had no ef fect lan the completion of second meiosis or first division, However, microinjection of these antibodies during the early pronucleate phase prior to S-phase onset blocked uptake of the kinase into pronuclei and interfered with proper and timely cell cycle progression to first cle avage. These results suggest that the kinase regulates the progression from interphase to mitosis during the first cell cycle.