Tousled-like kinase functions with the chromatin assembly pathway regulating nuclear divisions.
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.
Carrera
Pilar
P
Abteilung Molekulare Entwicklungsbiologie, Max-Planck-Institut für biophysikalische Chemie, Am Fassberg, D-37077 Göttingen, Germany.
Moshkin
Yuri M
YM
Gronke
Sebastian
S
Sillje
Herman H W
HH
Nigg
Erich A
EA
Jackle
Herbert
H
Karch
Francois
F
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
D018797:Cell Cycle Proteins; D002843:Chromatin; D029721:Drosophila Proteins; D006657:Histones; C491642:asf1 protein, Drosophila; C498930:tlk protein, Drosophila; D017346:Protein Serine-Threonine Kinases