TY - JOUR
T1 - cdc18+ regulates initiation of DNA replication in Schizosaccharomyces pombe
AU - Muzi-Falconi, Marco
AU - Brown, Grant W.
AU - Kelly, Thomas J.
PY - 1996/2/20
Y1 - 1996/2/20
N2 - In the fission yeast Schizosaccharomyces pombe the cdc18+ gene is required both for initiation of DNA replication and for coupling mitosis to the completion of S phase. Cells lacking Cdc18 fail to enter S phase but still undergo nuclear division. Expression of cdcl8+ is sufficient to drive a G1-arrested cdc10(ts) mutant into the S phase of the cell cycle, indicating that cdc18+ represents a critical link between passage through START and the initiation of DNA replication. Here we show that Cdc18 is a highly unstable protein that is expressed only once per cell cycle at the boundary between G1 and S phase. De novo synthesis of Cdc18 is required before, but not after, the initiation of DNA replication, indicating that Cdc18 function is not necessary once the initiation event has occurred. Overproduction of the protein results in an accumulation of cells with DNA content of greater than 2C and delays mitosis, suggesting that Cdc18 is sufficient to cause reinitiation of DNA replication within a given cell cycle. Our data indicate that the synthesis of Cdc18 protein is a critical rate-limiting step in the initiation of DNA replication during each cell cycle. The extreme lability of the protein may contribute to the prevention of reinitiation.
AB - In the fission yeast Schizosaccharomyces pombe the cdc18+ gene is required both for initiation of DNA replication and for coupling mitosis to the completion of S phase. Cells lacking Cdc18 fail to enter S phase but still undergo nuclear division. Expression of cdcl8+ is sufficient to drive a G1-arrested cdc10(ts) mutant into the S phase of the cell cycle, indicating that cdc18+ represents a critical link between passage through START and the initiation of DNA replication. Here we show that Cdc18 is a highly unstable protein that is expressed only once per cell cycle at the boundary between G1 and S phase. De novo synthesis of Cdc18 is required before, but not after, the initiation of DNA replication, indicating that Cdc18 function is not necessary once the initiation event has occurred. Overproduction of the protein results in an accumulation of cells with DNA content of greater than 2C and delays mitosis, suggesting that Cdc18 is sufficient to cause reinitiation of DNA replication within a given cell cycle. Our data indicate that the synthesis of Cdc18 protein is a critical rate-limiting step in the initiation of DNA replication during each cell cycle. The extreme lability of the protein may contribute to the prevention of reinitiation.
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U2 - 10.1073/pnas.93.4.1566
DO - 10.1073/pnas.93.4.1566
M3 - Article
C2 - 8643672
AN - SCOPUS:0029864759
SN - 0027-8424
VL - 93
SP - 1566
EP - 1570
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
IS - 4
ER -