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1.
Cell ; 156(3): 413-27, 2014 Jan 30.
Article in English | MEDLINE | ID: mdl-24485452

ABSTRACT

The response to DNA damage, which regulates nuclear processes such as DNA repair, transcription, and cell cycle, has been studied thoroughly. However, the cytoplasmic response to DNA damage is poorly understood. Here, we demonstrate that DNA damage triggers dramatic reorganization of the Golgi, resulting in its dispersal throughout the cytoplasm. We further show that DNA-damage-induced Golgi dispersal requires GOLPH3/MYO18A/F-actin and the DNA damage protein kinase, DNA-PK. In response to DNA damage, DNA-PK phosphorylates GOLPH3, resulting in increased interaction with MYO18A, which applies a tensile force to the Golgi. Interference with the Golgi DNA damage response by depletion of DNA-PK, GOLPH3, or MYO18A reduces survival after DNA damage, whereas overexpression of GOLPH3, as is observed frequently in human cancers, confers resistance to killing by DNA-damaging agents. Identification of the DNA-damage-induced Golgi response reveals an unexpected pathway through DNA-PK, GOLPH3, and MYO18A that regulates cell survival following DNA damage.


Subject(s)
DNA Damage , DNA-Activated Protein Kinase/metabolism , Golgi Apparatus/metabolism , Membrane Proteins/metabolism , Myosins/metabolism , Amino Acid Sequence , Animals , Cell Line , Cell Survival , Cells, Cultured , Humans , Membrane Proteins/chemistry , Mice , Molecular Sequence Data , Phosphorylation , Rats , Sequence Alignment
2.
PLoS One ; 7(8): e43767, 2012.
Article in English | MEDLINE | ID: mdl-22937092

ABSTRACT

Biological invasions can cause major ecological and economic impacts. During the early stages of invasions, eradication is desirable but tactics are lacking that are both effective and have minimal non-target effects. Mating disruption, which may meet these criteria, was initially chosen to respond to the incursion of light brown apple moth, Epiphyas postvittana (LBAM; Lepidoptera: Tortricidae), in California. The large size and limited accessibility of the infested area favored aerial application. Moth sex pheromone formulations for potential use in California or elsewhere were tested in a pine forest in New Zealand where LBAM is abundant. Formulations were applied by helicopter at a target rate of 40 g pheromone per ha. Trap catch before and after application was used to assess the efficacy and longevity of formulations, in comparison with plots treated with ground-applied pheromone dispensers and untreated control plots. Traps placed at different heights showed LBAM was abundant in the upper canopy of tall trees, which complicates control attempts. A wax formulation and polyethylene dispensers were most effective and provided trap shut-down near ground level for 10 weeks. Only the wax formulation was effective in the upper canopy. As the pheromone blend contained a behavioral antagonist for LBAM, 'false trail following' could be ruled out as a mechanism explaining trap shutdown. Therefore, 'sensory impairment' and 'masking of females' are the main modes of operation. Mating disruption enhances Allee effects which contribute to negative growth of small populations and, therefore, it is highly suitable for area-wide control and eradication of biological invaders.


Subject(s)
Insect Control/methods , Pest Control, Biological/methods , Sex Attractants/administration & dosage , Sexual Behavior, Animal/drug effects , Animals , Moths , New Zealand
3.
Genetics ; 167(1): 203-6, 2004 May.
Article in English | MEDLINE | ID: mdl-15166147

ABSTRACT

The majority of genes of multicellular organisms encode proteins with functions that are not required for viability but contribute to important physiological functions such as behavior and reproduction. It is estimated that 75% of the genes of Drosophila melanogaster are nonessential. Here we report on a strategy used to establish a large collection of stocks that is suitable for the recovery of mutations in such genes. From approximately 72,000 F(3) cultures segregating for autosomes heavily treated with ethyl methanesulfonate (EMS), approximately 12,000 lines in which the treated second or third chromosome survived in homozygous condition were selected. The dose of EMS induced an estimated rate of 1.2-1.5 x 10(-3) mutations/gene and predicts five to six nonessential gene mutations per chromosome and seven to nine alleles per locus in the samples of 6000 second chromosomes and 6000 third chromosomes. Due to mosaic mutations induced in the initial exposure to the mutagen, many of the lines are segregating or are now fixed for lethal mutations on the mutagenized chromosome. The features of this collection, known as the Zuker collection, make it a valuable resource for forward and reverse genetic screens for mutations affecting a wide array of biological functions.


Subject(s)
Drosophila melanogaster/genetics , Genetic Techniques , Mutagenesis , Alleles , Animals , Chromosomes/ultrastructure , Crosses, Genetic , Databases as Topic , Ethyl Methanesulfonate , Genes, Lethal , Homozygote , Models, Genetic , Mutagens , Mutation
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