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Interaction between DUE-B and Treslin is required to load Cdc45 on chromatin in human cells



Interaction between DUE-B and Treslin is required to load Cdc45 on chromatin in human cells



Journal of Biological Chemistry 293(37): 14497-14506



A key step in the initiation of eukaryotic DNA replication is the binding of the activator protein Cdc45 to promote MCM helicase unwinding of the origin template. We show here that the c-myc origin DNA unwinding element-binding protein, DUE-B, interacts in HeLa cells with the replication initiation protein Treslin to allow Cdc45 loading onto chromatin. The chromatin loading of DUE-B and Treslin are mutually dependent, and the DUE-B-Treslin interaction is cell cycle-regulated to peak as cells exit G1 phase prior to the initiation of replication. The conserved C-terminal domain of DUE-B is required for its binding to TopBP1, Treslin, Cdc45, and the MCM2-7 complex, as well as for the efficient loading of Treslin, Cdc45, and TopBP1 on chromatin. These results suggest that DUE-B acts to identify origins by MCM binding and serves as a node for replication protein recruitment and Cdc45 transfer to the prereplication complex.

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Accession: 065247798

Download citation: RISBibTeXText

PMID: 30037903

DOI: 10.1074/jbc.ra118.004519


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