Chromosome DNA is replicated accurately in accordance with the cell cycle and segregated to daughter cells. This process ensures cells to transmit accurate genomic information to their progeny. However, molecular mechanism of DNA replication and its regulation in eukaryotic cell cycle have not been well elucidated. To approach this subject, we have isolated novel replication factors of budding yeast and analyzed their functions.

Eukaryotic chromosome is replicated exactly once in the S-phase of the cell cycle. Cyclin-dependent kinase (CDK), a key cell cycle engine, inhibits re-replication as well as promotes the initiation step of DNA replication. We have revealed that CDK promotes DNA replication through the phosphorylation-dependent interaction between replication proteins; Sld2 and Sld3 proteins are phosphorylated by CDK and then bind to Dpb11. Thus, if we bypass this interaction, DNA replicates without CDK activity. However, it is not elucidated how the interaction between these proteins promotes DNA replication. Therefore, we have been studying molecular mechanism of the initiation step in chromosomal DNA replication, which requires CDK activity.

Muramatsu, S., Hirai, K., Tak, Y-S., Kamimura, Y., and Araki, H. (2010). CDK-dependent complex formation between replication proteins, Dpb11, Sld2, Pol and GINS in budding yeast.Genes & Dev. 24, 602-612.

Tanaka, S., Tak, Y-S., and Araki, H. (2007). The role of CDK in the initiation step of DNA replication in eukaryotes. Cell Division 2, 16.

Tanaka, S., Umemori, T., Hirai, K., Muramatsu, S., Kamimura, Y. and Araki, H. (2007). CDK-dependent phosphorylation of Sld2 and Sld3 initiates DNA replication in budding yeast. Nature 445, 328-332.

Tak, Y-S., Tanaka, Y., Endo, S., Kamimura, Y. and Araki, H. (2006). A CDK-catalysed regulatory phosphorylation for formation of the DNA replication complex Sld2-Dpb11. EMBO J. 25, 1987-1996.

Walter, J. C. and Araki, H. (2006). Activation of pre-replication complexes. In DNA Replication and Human Disease (ed. DePamphilis, M. L.), pp. 89-104, Cold Spring Harbor Laboratory Press, NY.

Iida, T. and Araki, H. (2004). Non-competitive counteractions of DNA polymerase ε and ISW2/yCHRAC for epigenetic inheritance of telomere-position effect in Saccharomyces cerevisiae. Mol. Cell. Biol. 24, 217-227