TLKs (tousled-like kinases) belong to a conserved serine/ threonine kinase family in multicellular organisms. Studies in flies and humans showed that TLKs function in chromatin assembly at S phase and chromosome condensation at M phase during cell cycle (1, 2). Recent studies showed that C. elegans
tlk-1 plays an essential role in transcription (3). We found that
tlk-1 is also important for chromosome condensation and segregation during mitosis.
tlk-1(RNAi) mutants showed aneuploidy in DNA content and arrested at an approximately 55-cell stage with uneven distribution of small and large nuclei. To further characterize the
tlk-1(RNAi) phenotype, we used the XA3505 strain carrying GFP-tagged histone H2B and TBB-2 to monitor DNA and tubulin dynamics during mitosis in living embryos. Prometaphase chromosomes of
tlk-1(RNAi) embryos did not condense to a rod-like shape as those of wild-type embryos did. Although metaphase chromosomes of
tlk-1(RNAi) mutants aligned in the metaphase plate but did not condense properly. Chromosome bridges and unequal (or even no) chromosome segregation were frequently observed during anaphase. These results show that
tlk-1 is important for DNA condensation and segregation during mitosis. We are currently performing a yeast two-hybrid screen and
tlk-1 suppressor screen to identify molecules that may directly or indirectly interact with
tlk-1 during mitosis. References: 1.Carrera, P., Moshkin, Y.M., Gronke, S., Sillje, H.H.W., Nigg, E.A., Jackle, H., and Karch, F. (2003) Genes & Dev., 17, 2578-2590. 2.Li, Y., DeFatta, R., Anthony, C., Sunavala, G., and DeBenedetti, A. (2001) Oncogene, 20, 726-738. 3.Han, Z., Saam J.R., Adams, H.P., Mango S.E., and Schumacher, J.M. (2003) Curr. Biol., 13, 1921-1929.