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Originally published as Genetics Published Articles Ahead of Print on February 1, 2006.
Genetics, Vol. 172, 2367-2377, April 2006, Copyright © 2006
doi:10.1534/genetics.105.042473
Mutations in the extra sex combs and Enhancer of Polycomb Genes Increase Homologous Recombination in Somatic Cells of Drosophila melanogaster
Angela M. Holmes, Kelly A. Weedmark and Gregory B. Gloor1
Department of Biochemistry, Schulich School of Medicine and Dentistry, The University of Western Ontario, London, Ontario N6A 5C1, Canada
1 Corresponding author: Department of Biochemistry, Schulich School of Medicine and Dentistry, The University of Western Ontario, London, ON N6A 5C1, Canada.
E-mail: ggloor{at}uwo.ca
We found that heterozygous mutant alleles of E(Pc) and esc increased homologous recombination from an allelic template in somatic cells in a P-element-induced double-strand break repair assay. Flies heterozygous for mutant alleles of these genes showed increased genome stability and decreased levels of apoptosis in imaginal discs and a concomitant increase in survival following ionizing radiation. We propose that this was caused by a genomewide increase in homologous recombination in somatic cells. A double mutant of E(Pc) and esc had no additive effect, showing that these genes act in the same pathway. Finally, we found that a heterozygous deficiency for the histone deacetylase, Rpd3, masked the radiation-resistant phenotype of both esc and E(Pc) mutants. These findings provide evidence for a gene dosage-dependent interaction between the esc/E(z) complex and the Tip60 histone acetyltransferase complex. We propose that esc and E(Pc) mutants enhance homologous recombination by modulating the histone acetylation status of histone H4 at the double-strand break.
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