Treslin Collaborates with TopBP1 in Triggering the Initiation of DNA Replication

SummaryTopBP1 has important roles in both DNA replication and checkpoint regulation in vertebrates. We have identified a protein called Treslin that associates with TopBP1 in Xenopus egg extracts. Depletion of Treslin from egg extracts strongly inhibits chromosomal DNA replication. Binding of Treslin to chromatin in egg extracts occurs independently of TopBP1. However, loading of the initiator protein Cdc45 onto chromatin cannot take place in the absence of Treslin. Prior to the initiation of DNA replication, Treslin associates with TopBP1 in a Cdk2-dependent manner. Ablation of Treslin from human cells also strongly inhibits DNA replication. Taken together, these results indicate that Treslin and TopBP1 collaborate in the Cdk2-mediated loading of Cdc45 onto replication origins. Thus, Treslin regulates a pivotal step in the initiation of DNA replication in vertebrates.

Graphical AbstractFigure optionsDownload high-quality image (402 K)Download as PowerPoint slideHighlights
► Treslin is a newly identified factor for initiation of vertebrate DNA replication
► Treslin interacts with TopBP1, a protein required for initiation of DNA replication
► Association of Treslin and TopBP1 requires cyclin-dependent kinase activity
► Treslin and TopBP1 collaborate in loading the initiator protein Cdc45 onto DNA