Mutations in the extra sex combs and Enhancer of Polycomb genes increase homologous recombination in somatic cells of Drosophila melanogaster.
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.
Holmes
Angela M
AM
Department of Biochemistry, Schulich School of Medicine and Dentistry, The University of Western Ontario, London, Ontario N6A 5C1, Canada.
Weedmark
Kelly A
KA
Gloor
Gregory B
GB
D000107:Acetylation; D000818:Animals; D002868:Chromosomal Proteins, Non-Histone / Q000235:genetics*; D003433:Crosses, Genetic; D004260:DNA Repair; D029721:Drosophila Proteins / Q000235:genetics*; D004331:Drosophila melanogaster / Q000235:genetics*; D018628:Gene Dosage; D006579:Heterozygote; D056284:Histone Deacetylase 1; D006655:Histone Deacetylases / Q000378:metabolism; D011495:Histone-Lysine N-Methyltransferase; D006657:Histones / Q000737:chemistry; D009154:Mutation; D063150:Polycomb Repressive Complex 1; D063151:Polycomb Repressive Complex 2; D011995:Recombination, Genetic; D012097:Repressor Proteins / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism; D019076:Transgenes
D002868:Chromosomal Proteins, Non-Histone; D029721:Drosophila Proteins; C115870:E(Pc) protein, Drosophila; D006657:Histones; C066770:Pc protein, Drosophila; D012097:Repressor Proteins; D014157:Transcription Factors; D011495:Histone-Lysine N-Methyltransferase; D063151:Polycomb Repressive Complex 2; C543389:esc protein, Drosophila; D063150:Polycomb Repressive Complex 1; C512966:HDAC1 protein, Drosophila; D056284:Histone Deacetylase 1; D006655:Histone Deacetylases