title: Mutations in the extra sex combs and Enhancer of Polycomb genes increase homologous recombination in somatic cells of Drosophila melanogaster.
abstract: 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.
authors.affiliation: Department of Biochemistry, Schulich School of Medicine and Dentistry, The University of Western Ontario, London, Ontario N6A 5C1, Canada.
authors.forename: Angela M
authors.initials: AM
authors.lastname: Holmes
authors.forename: Kelly A
authors.initials: KA
authors.lastname: Weedmark
authors.forename: Gregory B
authors.initials: GB
authors.lastname: Gloor
mesh_terms: 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
chemical_list: 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