Direct regulation of Treslin by cyclin-dependent kinase is essential for the onset of DNA replication

• DOI: 10.1083/jcb.201102003
• Publication Date: 2011-06-07T04:30:41Z
• Authors: Akiko Kumagai; Anna Shevchenko; Andrej Shevchenko; William G. Dunphy
• Keywords: Origin recognition complex; Licensing factor; Cyclin A; Replication protein A; Pre-replication complex; Replication factor C

Treslin, a TopBP1-interacting protein, is necessary for deoxyribonucleic acid (DNA) replication in vertebrates. Association between Treslin and TopBP1 requires cyclin-dependent kinase (Cdk) activity Xenopus laevis egg extracts. We investigated the mechanism functional importance of Cdk this interaction using both X. extracts human cells. found that also associated with Cdk-regulated manner cells was phosphorylated within conserved consensus target sequence (on S976 S1000 humans). Recombinant Cdk2–cyclin E residue vitro very effectively. Moreover, mutant cannot undergo phosphorylation on site showed significantly diminished binding to TopBP1. Finally, harboring were severely deficient DNA replication. Collectively, these results indicate Cdk-mediated during S phase its effective association ability promote