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Expression of Cdc18/Cdc6 and Cdt1 during G 2 phase induces initiation of DNA replication
Author(s) -
Yanow Stephanie K.,
Lygerou Zoi,
Nurse Paul
Publication year - 2001
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1093/emboj/20.17.4648
Subject(s) - dna replication factor cdt1 , origin recognition complex , biology , dna re replication , licensing factor , control of chromosome duplication , pre replication complex , dna replication , eukaryotic dna replication , cell cycle , microbiology and biotechnology , s phase , origin of replication , dna synthesis , chromatin , replication factor c , dna , genetics , cell
Cdc18/Cdc6 and Cdt1 are essential initiation factors for DNA replication. In this paper we show that expression of Cdc18 in fission yeast G 2 cells is sufficient to override the controls that ensure one S phase per cell cycle. Cdc18 expression in G 2 induces DNA synthesis by re‐firing replication origins and recruiting the MCM Cdc21 to chromatin in the presence of low levels of Cdt1. However, when Cdt1 is expressed together with Cdc18 in G 2 , cells undergo very rapid, uncontrolled DNA synthesis, accumulating DNA contents of 64 C or more. Our data suggest that Cdt1 may potentiate re‐replication by inducing origins to fire more persistently, possibly by stabilizing Cdc18 on chromatin. In addition, low level expression of a mutant form of Cdc18 that cannot be phosphorylated by cyclin‐dependent kinases is not sufficient to induce replication in G 2 , but does so only when co‐expressed with Cdt1. Thus, regulation of both Cdc18 and Cdt1 in G 2 plays a crucial role in preventing the re‐initiation of DNA synthesis until the next cell cycle.