Crystal Structure of the Homology Domain of the Eukaryotic DNA Replication Proteins Sld3/Treslin

The initiation of eukaryotic chromosomal DNA replication requires the formation of an active replicative helicase at the replication origins of chromosomal DNA. Yeast Sld3 and its metazoan counterpart Treslin are the hub proteins mediating protein associations critical for the helicase formation. Here, we show the crystal structure of the central domain of Sld3 that is conserved in Sld3/Treslin family of proteins. The domain consists of two segments with 12 helices and is sufficient to bind to Cdc45, the essential helicase component. The structure model of the Sld3-Cdc45 complex, which is crucial for the formation of the active helicase, is proposed. [Display omitted] •Structure of the domain conserved in Sld3/Treslin is essential for DNA replication•Rhombic-shaped compact domain is sufficient for the binding with Cdc45•Two segments are important for maintaining stable binding with Cdc45•The model of Sld3-Cdc45 complex crucial for initiating eukaryotic DNA replication is proposed The Sld3/Treslin proteins mediate protein associations that are critical for active DNA replicative helicase formation in eukaryotic cells. Itou et al. structurally and functionally analyze a conserved Sld3/Treslin domain, informing a model of the Sld3-Cdc45 complex that is essential for the process.