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Published February 5, 2010 | public
Journal Article

Treslin Collaborates with TopBP1 in Triggering the Initiation of DNA Replication

Abstract

TopBP1 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.

Additional Information

© 2010 Elsevier Inc. Received 28 May 2009; revised 14 October 2009; accepted 22 December 2009. Published online: January 28, 2010. Available online 28 January 2010. We are grateful to laboratory members for comments on the manuscript. We would also like to thank Rochelle Diamond for assistance with the FACS analyses and T.C. Spelsberg (Mayo Clinic) for the U2OS T-REx cells. This work was supported by National Institutes of Health grants GM043974 and GM070891 to W.G.D.

Additional details

Created:
August 21, 2023
Modified:
October 20, 2023