Stable association of mitotic cyclin B/Cdc2 to replication origins prevents endoreduplication.
We show that in fission yeast the mitotic B type cyclin Cdc13/Cdc2 kinase associates with replication origins in vivo. This association is dependent on the origin recognition complex (ORC), is established as chromosomes are replicated, and is maintained during G2 and early mitosis. Cells expressing an orp2 (ORC2) allele that reduces binding of Cdc13 to replication origins are acutely prone to chromosomal reduplication. In synchronized endoreduplicating cells, following Cdc13 ablation, replication origins are coordinately licensed prior to each successive round of S phase with the same periodicity as in a normal cell cycle. Thus, ORC bound mitotic Cyclin B/Cdc2 kinase imposes the dependency of S phase on an intervening mitosis but not the temporal licensing of replication origins between each S phase.
Wuarin
Jérôme
J
Division of Yeast Genetics, National Institute for Medical Research, The Ridgeway, Mill Hill, London NW7 1AA, United Kingdom.
Buck
Vicky
V
Nurse
Paul
P
Millar
Jonathan B A
JB
D016203:CDC2 Protein Kinase / Q000378:metabolism*; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism*; D015825:Chromosomes, Fungal / Q000378:metabolism; D019926:Cyclin B / Q000378:metabolism*; D016213:Cyclins / Q000235:genetics / Q000378:metabolism; D004271:DNA, Fungal / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D005656:Fungal Proteins / Q000235:genetics / Q000378:metabolism*; D064148:Minichromosome Maintenance Complex Component 4; D008938:Mitosis; D051738:Origin Recognition Complex; D010766:Phosphorylation; D011401:Promoter Regions, Genetic; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D018741:Replication Origin; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism; D012568:Schizosaccharomyces / Q000235:genetics / Q000378:metabolism; D029702:Schizosaccharomyces pombe Proteins; D034501:Telomere-Binding Proteins / Q000378:metabolism
C452219:Cdc13 protein, S cerevisiae; D018797:Cell Cycle Proteins; C080328:Cig2 protein, S pombe; D019926:Cyclin B; D016213:Cyclins; D004271:DNA, Fungal; D004268:DNA-Binding Proteins; D005656:Fungal Proteins; D051738:Origin Recognition Complex; D011993:Recombinant Fusion Proteins; D029701:Saccharomyces cerevisiae Proteins; D029702:Schizosaccharomyces pombe Proteins; C499592:TAH11 protein, S cerevisiae; D034501:Telomere-Binding Proteins; C082462:cdc18 protein, S pombe; C406818:cdt1 protein, S pombe; C097339:orc1 protein, S pombe; C097704:orc2 protein, S pombe; D016203:CDC2 Protein Kinase; C092802:MCM4 protein, S cerevisiae; D064148:Minichromosome Maintenance Complex Component 4