title: Positional cloning of a cyromazine resistance gene in Drosophila melanogaster.
abstract: Cyromazine is an effective insecticide used to control dipteran insects. Its precise mode of action is yet to be determined, although it has been suggested that it interferes with the hormone system, sclerotization of the cuticle, or nucleic acid metabolism. To understand the way in which cyromazine acts, we have positionally cloned a cyromazine resistance gene from Drosophila melanogaster. Six cyromazine resistance alleles had previously been generated by ethyl methanasulphonate treatment. Two of these failed to complement each other and here we identify them as having independent non-sense mutations in CG32743, which is an ortholog of Smg1 of worms and mammals and encodes a phosphatidylinositol kinase-like kinase (PIKK). RNAi experiments confirm that cyromazine resistance can be achieved by knocking down CG32743. These are the first cyromazine resistant mutations identified at the nucleotide level. In mammals Smg1 phosphorylates P53 in response to DNA damage. This finding supports the hypothesis that cyromazine interferes with nucleic acid metabolism.
authors.affiliation: Centre for Environmental Stress and Adaptation Research, Department of Genetics, The University of Melbourne, VIC 3010, Australia.
authors.forename: Z
authors.initials: Z
authors.lastname: Chen
authors.forename: C
authors.initials: C
authors.lastname: Robin
authors.forename: J
authors.initials: J
authors.lastname: Damiano
authors.forename: J
authors.initials: J
authors.lastname: Lydall
authors.forename: C
authors.initials: C
authors.lastname: Lumb
authors.forename: K
authors.initials: K
authors.lastname: Smith
authors.forename: A
authors.initials: A
authors.lastname: Blasetti
authors.forename: P J
authors.initials: PJ
authors.lastname: Daborn
authors.forename: D
authors.initials: D
authors.lastname: Heckel
authors.forename: J A
authors.initials: JA
authors.lastname: McKenzie
authors.forename: P
authors.initials: P
authors.lastname: Batterham
mesh_terms: D000483:Alleles; D000818:Animals; D003001:Cloning, Molecular; D029721:Drosophila Proteins / Q000737:chemistry / Q000235:genetics*; D004331:Drosophila melanogaster / Q000235:genetics*; D005260:Female; D017344:Genes, Insect; D007305:Insecticide Resistance / Q000235:genetics; D008297:Male; D009154:Mutation; D017346:Protein Serine-Threonine Kinases / Q000737:chemistry / Q000235:genetics*; D034622:RNA Interference; D017386:Sequence Homology, Amino Acid; D014227:Triazines
chemical_list: D029721:Drosophila Proteins; D014227:Triazines; C028704:cyromazine; D017346:Protein Serine-Threonine Kinases; C510482:nonC protein, Drosophila