CDK-dependent carrier formation is essential for the initiation of DNA replication. Genes and Development Araki Laboratory, Division of Microbial Genetics CDK-dependent complex formation between replication proteins Dpb11, Sld2, Polε, and GINS in budding yeast. achiko Muramatsu, Kazuyuki Hirai, Yon-Soo Tak, Yoichiro Kamimura, and Hiroyuki Araki, Genes and Dev., 24, 602-612, 2010.　doi:10.1101/gad.1883410 　Eukaryotic chromosomal DNA replication requires cyclin-dependent kinase (CDK) activity. CDK phosphorylates two yeast replication proteins, Sld3 and Sld2, which both bind to Dpb11 when phosphorylated. These phosphorylation-dependent interactions are essential and are the minimal requirements for CDK-dependent activation of DNA replication. However, how these interactions activate DNA replication has not been elucidated. This study reaveled that CDK promotes the formation of a newly identified fragile complex, the pre-loading complex (pre-LC) containing DNA polymeraseε(Polε, GINS, Sld2 and Dpb11. Formation of the pre-LC requires phosphorylation of Sld2 by CDK, but is independent of DNA replication, protein association with replication origins, and Dbf4-dependent Cdc7 kinase, which is also essential for the activation of DNA replication. Thus, CDK seems to regulate the initiation of DNA replication in budding yeast through formation of the pre-LC. The authors further proposed that the pre-LC works as a carrier for GINS to associate with replication origins. ←Back