DNA repair and transcriptional effects of mutations in TFIIH in Drosophila development.
Mutations in XPB and XPD TFIIH helicases have been related with three hereditary human disorders: xeroderma pigmentosum, Cockayne syndrome, and trichothiodystrophy. The dual role of TFIIH in DNA repair and transcription makes it difficult to discern which of the mutant TFIIH phenotypes is due to defects in any of these different processes. We used haywire (hay), the Drosophila XPB homolog, to dissect this problem. Our results show that when hay dosage is affected, the fly shows defects in structures that require high levels of transcription. We found a genetic interaction between hay and cdk7, and we propose that some of these phenotypes are due to transcriptional deficiencies. We also found more apoptotic cells in imaginal discs and in the CNS of hay mutant flies than in wild-type flies. Because this abnormal level of apoptosis was not detected in cdk7 flies, this phenotype could be related to defects in DNA repair. In addition the apoptosis induced by p53 Drosophila homolog (Dmp53) is suppressed in heterozygous hay flies.
Merino
Carlos
C
Department of Genetics and Molecular Physiology, Institute of Biotechnology, Universidad Nacional Autónoma de México, Morelos 62250, México.
Reynaud
Enrique
E
Vázquez
Martha
M
Zurita
Mario
M
D000483:Alleles; D000818:Animals; D030801:Animals, Genetically Modified; D015153:Blotting, Western; D018844:Cyclin-Dependent Kinases / Q000235:genetics / Q000378:metabolism; D004260:DNA Repair; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D004330:Drosophila / Q000196:embryology* / Q000235:genetics; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D009154:Mutation; D009693:Nucleic Acid Hybridization; D010641:Phenotype; D012313:RNA / Q000378:metabolism; D035381:TATA-Binding Protein Associated Factors; D035362:Transcription Factor TFIID; D051758:Transcription Factor TFIIH; D019473:Transcription Factors, TFII / Q000235:genetics* / Q000378:metabolism; D014158:Transcription, Genetic; D016159:Tumor Suppressor Protein p53 / Q000235:genetics; D014466:Ultraviolet Rays; D014921:Wings, Animal / Q000196:embryology; D000095043:Cyclin-Dependent Kinase-Activating Kinase
D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; D035381:TATA-Binding Protein Associated Factors; C084976:Taf6 protein, Drosophila; D035362:Transcription Factor TFIID; D019473:Transcription Factors, TFII; D016159:Tumor Suppressor Protein p53; D051758:Transcription Factor TFIIH; C078672:hay protein, Drosophila; D012313:RNA; D018844:Cyclin-Dependent Kinases; D000095043:Cyclin-Dependent Kinase-Activating Kinase