Chk1 and Wee1 kinases coordinate DNA replication, chromosome condensation and anaphase entry

• Author(s) / Creator(s)

  • Campbell, S.D.
  • Homola, E.M.
  • Fasulo, B.
  • Yu, K.R.
  • Hsieh, T.S.
  • Sullivan, W.
  • Koyama, C.

• Defects in DNA replication and chromosome condensation are common phenotypes in cancer cells. A link between replication and condensation has been established, but little is known about the role of checkpoints in monitoring chromosome condensation. We investigate this function by live analysis, using the rapid division cycles in the early Drosophila embryo. We find that S-phase and topoisomerase inhibitors delay both the initiation and the rate of chromosome condensation. These cell cycle delays are mediated by the cell cycle kinases chk1 and wee1. Inhibitors that cause severe defects in chromosome condensation and congression on the metaphase plate result in delayed anaphase entry. These delays are mediated by wee1 and are not the result of spindle assembly checkpoint activation. In addition, we provide the first detailed live analysis of the direct effect of widely used anticancer agents (aclarubicin, ICRF-193, VM26, doxorubicin, camptothecin, aphidicolin, hydroxyurea, cisplatin, mechlorethamine and x-rays) on key nuclear and cytoplasmic cell cycle events.

• Date created

  2012

• Subjects / Keywords

  • Drosophila-melanogaster
  • Nuclear
  • Phosphorylation
  • Topoisomerase-II
  • Polo-like kinase-1
  • Human-cells
  • Damage checkpoint
  • Activation
  • Mitotic entry
  • Early embryogenesis

• Type of Item

  Article (Published)

• DOI

  https://doi.org/10.7939/R39P29

• License

  © 2012 Fasulo et al. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0).