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Division of Microbial Genetics • Araki Group

Molecular mechanism of eukaryotic DNA replication in the cell cycle

Professor 　　　　　 ARAKI, Hiroyuki hiaraki
Assistant Professor 　 TANAKA, Seiji　 setanaka
Assistant Professor HIZUME, Kohji　　 khizume

Homepage URL : http://www.nig.ac.jp/labs/MicGen/index.html

　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.

Initiation of DNA replication. When CDK is activated from G1/S boundary, Sld2 and Sld3 are phosphorylated and bind to Dpb11. These interactions promote assembly of replication proteins including DNA polymerases to origins and then DNA replication starts.

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

Tanaka, S., and Araki, H. (2010) Regulation of the initiation step of DNA replication by cyclin-dependent kinases. Chromosoma 119, 565-574.

Suzuki, Y., Higuchi, Y., Hizume, K., Yokokawa, M., Yoshimura, S.H., Yoshikawa, K., and Takeyasu, K. (2010). Molecular dynamics of DNA and nucleosomes in solution studied by fast-scanning atomic force microscopy.
Ultramicroscopy 110, 682-688.

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, M. L. DePamphilis, ed. (New York, USA: Cold Spring Harbor Laboratory Press), pp. 89-104,.


Professor ARAKI, Hiroyuki hiaraki	Assistant Professor TANAKA, Seiji setanaka	Assistant Professor HIZUME, Kohji khizume

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