title: Tousled-like kinase functions with the chromatin assembly pathway regulating nuclear divisions.
abstract: Tousled-like kinases (TLKs) constitute a family of serine/threonine kinases conserved in plants and animals that act in a cell cycle-dependent manner. In mammals, their activity peaks during S phase, when they phosphorylate the antisilencing function protein 1 (ASF1), a histone chaperone involved in replication-dependent chromatin assembly. Here, we show that Drosophila ASF1 is also a phosphorylation target of TLK, and that the two components cooperate to control chromatin replication in vivo. By altering TLK activity through loss-of-function mutations, we show that nuclear divisions are arrested at interphase, followed by apoptosis. Overexpression of TLK alters the chromatin structure, suggesting that TLK mediates the activity of chromatin proteins. These results suggest that TLK coordinates cell cycle progression through the regulation of chromatin dynamics.
authors.affiliation: Abteilung Molekulare Entwicklungsbiologie, Max-Planck-Institut für biophysikalische Chemie, Am Fassberg, D-37077 Göttingen, Germany.
authors.forename: Pilar
authors.initials: P
authors.lastname: Carrera
authors.forename: Yuri M
authors.initials: YM
authors.lastname: Moshkin
authors.forename: Sebastian
authors.initials: S
authors.lastname: Gronke
authors.forename: Herman H W
authors.initials: HH
authors.lastname: Sillje
authors.forename: Erich A
authors.initials: EA
authors.lastname: Nigg
authors.forename: Herbert
authors.initials: H
authors.lastname: Jackle
authors.forename: Francois
authors.initials: F
authors.lastname: Karch
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D018797:Cell Cycle Proteins / Q000378:metabolism; D002455:Cell Division / Q000502:physiology*; D002843:Chromatin / Q000502:physiology*; D053938:DNA Fragmentation / Q000502:physiology; D004261:DNA Replication / Q000502:physiology; D004330:Drosophila / Q000235:genetics / Q000378:metabolism; D029721:Drosophila Proteins; D006657:Histones; D008969:Molecular Sequence Data; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D016415:Sequence Alignment
chemical_list: D018797:Cell Cycle Proteins; D002843:Chromatin; D029721:Drosophila Proteins; D006657:Histones; C491642:asf1 protein, Drosophila; C498930:tlk protein, Drosophila; D017346:Protein Serine-Threonine Kinases