Genetic screen for genes involved in Chk2 signaling in Drosophila.
Chk2 is a well characterized protein kinase with key roles in the DNA damage response. Chk2 is activated by phosphorylation following DNA damage, and relays that signal to various substrate proteins to induce cell cycle arrest, DNA repair, and apoptosis. In order to identify novel components of the Chk2 signaling pathway in Drosophila, we screened 2,240 EP misexpression lines for dominant modifiers of an adult rough eye phenotype caused by Chk2 overexpression in postmitotic cells of the eye imaginal disc. The rough eye phenotype was suppressed by mutation of the ATM kinase, a well-described activator of Chk2. Twenty-five EP modifiers were identified (three enhancers and 22 suppressors), none of which correspond to previously known components of Chk2 signaling. Three EPs caused defects in G2 arrest after irradiation with incomplete penetrance when homozygous, and are likely directly involved in the response to DNA damage. Possible roles for these modifiers in the DNA damage response and Chk2 signaling are discussed.
Park
Suk-Young
SY
Ilsong Institute of Life Science, Hallym University, Anyang, Korea.
Song
Young-Han
YH
D000818:Animals; D064447:Checkpoint Kinase 2; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000166:cytology / Q000201:enzymology* / Q000235:genetics*; D005124:Eye Abnormalities / Q000235:genetics; D016195:G2 Phase; D017344:Genes, Insect; D016153:Genes, Suppressor; D005820:Genetic Testing; D016678:Genome; D016254:Mutagenesis, Insertional; D010641:Phenotype; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction
D029721:Drosophila Proteins; D064447:Checkpoint Kinase 2; D017346:Protein Serine-Threonine Kinases; C112435:lok protein, Drosophila