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Regulation of initiation of division in Saccharomyces cerevisiae: characterization of the role of DCR2, GID8, and KEM1 in completion of START
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The decision to initiate division is very important, as once cells have initiated division they are committed to complete it. In Saccharomyces cerevisiae, commitment to a new round of cell division occurs at a regulatory point in late G1 called START. Progression through START requires the activation of the cyclin dependent kinase Cdc28p by the G1 cyclins. G1 cyclins in complex with Cdc28p activate the transcription of approximately 100 genes involved in the G1 to S transition and degradation of Sic1p, an inhibitor of B type cyclins, and thus are important for initiation of DNA replication. Despite the widely studied role of regulatory cyclins and cyclin dependent kinase in the G1 to S transition, how cells determine when to initiate DNA replication is poorly understood. We have identified several gene products, which when overexpressed, cause cells to initiate DNA replication faster than wild type. Here we discuss the role of DCR2 (Dosage dependent Cell cycle Regulator), GID8 (Glucose Induced Degradation) and KEM1 (Kar-Enhancing Mutation) in the regulation of START. Over expression of DCR2 and GID8 accelerates initiation of DNA replication. Cells lacking both these genes delay initiation of DNA replication. Genetic analysis suggests that Gid8p functions upstream of Dcr2p to promote START. Further, we show that DCR2, which codes for a metallo-phosphoesterase, might regulate completion of START by affecting degradation of Sic1p. Over expression of DCR2 lowers the half-life of Sic1p without altering the expression of Cln2p. The evidence suggests that Dcr2p affects START completion through dephosphorylation of Sic1p. KEM1 is a Saccharomyces cerevisiae gene, conserved in all eukaryotes, which codes for a 5Ã¢ÂÂ-3Ã¢ÂÂ cytoplasmic exonuclease. This exonuclease is involved in exiting mitosis, by degrading the mRNA of the mitotic cyclin CLB2. Besides its role in mitotic exit, an enzymatically inactive version of Kem1p can accelerate the G1 to S transition and initiation of DNA replication when over expressed. This result suggests that Kem1p might have a previously unrecognized role in the G1 to S transition independent of its exonuclease activity, and supports the notion that Kem1p is a multifunctional protein with distinct and separable roles.
Pathak, Ritu (2006). Regulation of initiation of division in Saccharomyces cerevisiae: characterization of the role of DCR2, GID8, and KEM1 in completion of START. Doctoral dissertation, Texas A&M University. Texas A&M University. Available electronically from