Eukaryotic chromosome DNA is replicated exactly only once per cell cycle and segregated to daughter cells. This process ensures cells to transmit accurate genomic information to their progeny. Eukaryotic DNA replication initiates from multiple sites, called replication origins, scattered throughout chromosomes and this initiation process is strictly regulated by the cell cycle. 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.
(A) AFM image of ORC-chromatin complexes. ORC (origin recognition complex) binds to replication origins, where DNA replication is initiated. We revealed that chromatin structure stabilizes origin-ORC interaction. (B) Origin association of the low abundance replication proteins Sld3, Sld7, and Cdc45 is the key to determining the temporal order of origin firing. Simultaneous over-expression of these proteins (“ON” in the figure) allows the late-firing origins to fire earlier in S phase (arrow in the figure).
Tanaka, S., and Araki, H. (2016). Role of CDK in replication initiation. In “The initiation of DNA replication in eukaryotes (ed. D. Kaplan)”, pp. 263-278.
Itou, H., Muramatsu, S., Shirakihara, Y., and Araki, H. (2014). Crystal Structure of the homology domain of the eukaryotic DNA replication proteins Sld3/Treslin. Structure 22, 1341-1347.
Hizume, K., Yagura, M., and Araki, H. (2013). Concerted interaction between origin recognition complex (ORC), nucleosomes and replication origin DNA ensures stable ORC-origin binding. Genes Cells 18, 764-779.