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Mammalian homologues of the plant Tousled gene code for cell-cycle-regulated kinases with maximal activities linked to ongoing DNA replication

Silljé, H. H. and Takahashi, K. and Tanaka, K. and Van Houwe, G. and Nigg, E. A.. (1999) Mammalian homologues of the plant Tousled gene code for cell-cycle-regulated kinases with maximal activities linked to ongoing DNA replication. The EMBO journal, Vol. 18, H. 20. pp. 5691-5702.

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Official URL: http://edoc.unibas.ch/dok/A5249425

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Abstract

The Tousled (TSL) gene of the plant Arabidopsis thaliana encodes a serine/threonine kinase that is essential for proper flower development. Here we report the cloning and characterization of two human putative homologues of the Arabidopsis TSL gene, termed TLK1 and TLK2 (Tousled-like kinase). At the protein level, the two human Tlks share 84% sequence similarity with each other and almost 50% with Arabidopsis Tsl. Furthermore, nuclear localization signals and predicted coiled-coil regions are conserved in the N-terminal domains of all three kinases. The mammalian Tlks share several functional properties with plant Tsl, including a broad expression, a propensity to dimerize and autophosphorylate, and a preference for similar substrates. Most interestingly, human Tlks are cell-cycle-regulated enzymes, displaying maximal activities during S phase. Whereas protein levels are virtually constant throughout the cell cycle, both Tlks appear to be regulated by cell-cycle-dependent phosphorylation. Drug-induced inhibition of DNA replication causes a rapid loss of Tlk activity, indicating that Tlk function is tightly linked to ongoing DNA replication. These findings provide the first biochemical clues as to the possible molecular functions of Tlks, a highly conserved family of kinases implicated in the development of multicellular organisms.
Faculties and Departments:05 Faculty of Science > Departement Biozentrum
05 Faculty of Science > Departement Biozentrum > Former Organization Units Biozentrum > Cell Biology (Nigg)
UniBasel Contributors:Nigg, Erich A.
Item Type:Article, refereed
Article Subtype:Research Article
Bibsysno:Link to catalogue
Publisher:Nature Publishing Group
ISSN:0261-4189
Note:Publication type according to Uni Basel Research Database: Journal article
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Last Modified:22 Mar 2012 14:19
Deposited On:22 Mar 2012 13:17

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