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J Cell Biol 2011 Jun 13;1936:995-1007. doi: 10.1083/jcb.201102003.
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Direct regulation of Treslin by cyclin-dependent kinase is essential for the onset of DNA replication.

Kumagai A , Shevchenko A , Shevchenko A , Dunphy WG .

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

PubMed ID: 21646402
PMC ID: PMC3115804
Article link: J Cell Biol
Grant support: [+]

Species referenced: Xenopus laevis
Genes referenced: cdc45 cdk2 myc tbx2 ticrr topbp1 znrd2

Article Images: [+] show captions
References [+] :
Araki, Cyclin-dependent kinase-dependent initiation of chromosomal DNA replication. 2010, Pubmed