title: Chk1 and Wee1 kinases coordinate DNA replication, chromosome condensation, and anaphase entry.
abstract: 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.
authors.affiliation: Sinsheimer Laboratories, Department of Molecular, Cellular and Developmental Biology, University of California, Santa Cruz, Santa Cruz, CA 95064, USA. fasulo@biology.ucsc.edu
authors.forename: Barbara
authors.initials: B
authors.lastname: Fasulo
authors.forename: Carol
authors.initials: C
authors.lastname: Koyama
authors.forename: Kristina R
authors.initials: KR
authors.lastname: Yu
authors.forename: Ellen M
authors.initials: EM
authors.lastname: Homola
authors.forename: Tao S
authors.initials: TS
authors.lastname: Hsieh
authors.forename: Shelagh D
authors.initials: SD
authors.lastname: Campbell
authors.forename: William
authors.initials: W
authors.lastname: Sullivan
mesh_terms: D000705:Anaphase; D000818:Animals; D018797:Cell Cycle Proteins / Q000378:metabolism*; D000071877:Checkpoint Kinase 1; D002875:Chromosomes / Q000378:metabolism*; D004261:DNA Replication; D004331:Drosophila melanogaster / Q000166:cytology / Q000196:embryology; D009685:Nuclear Envelope / Q000378:metabolism; D009687:Nuclear Proteins / Q000378:metabolism*; D011494:Protein Kinases / Q000378:metabolism*; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D016196:S Phase; D059003:Topoisomerase Inhibitors / Q000494:pharmacology
chemical_list: D018797:Cell Cycle Proteins; D009687:Nuclear Proteins; D059003:Topoisomerase Inhibitors; D011494:Protein Kinases; D011505:Protein-Tyrosine Kinases; C508847:Wee1 protein, Drosophila; D000071877:Checkpoint Kinase 1