title: Drosophila bloom helicase maintains genome integrity by inhibiting recombination between divergent DNA sequences.
abstract: DNA double strand breaks (DSB) can be repaired either via a sequence independent joining of DNA ends or via homologous recombination. We established a detection system in Drosophila melanogaster to investigate the impact of sequence constraints on the usage of the homology based DSB repair via single strand annealing (SSA), which leads to recombination between direct repeats with concomitant loss of one repeat copy. First of all, we find the SSA frequency to be inversely proportional to the spacer length between the repeats, for spacers up to 2.4 kb in length. We further show that SSA between divergent repeats (homeologous SSA) is suppressed in cell cultures and in vivo in a sensitive manner, recognizing sequence divergences smaller than 0.5%. Finally, we demonstrate that the suppression of homeologous SSA depends on the Bloom helicase (Blm), encoded by the Drosophila gene mus309. Suppression of homeologous recombination is a novel function of Blm in ensuring genomic integrity, not described to date in mammalian systems. Unexpectedly, distinct from its function in Saccharomyces cerevisiae, the mismatch repair factor Msh2 encoded by spel1 does not suppress homeologous SSA in Drosophila.
authors.affiliation: Insitut für Molekularbiologie der Universität Zürich, Zürich, Switzerland.
authors.forename: Michael
authors.initials: M
authors.lastname: Kappeler
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Kranz
authors.forename: Katrina
authors.initials: K
authors.lastname: Woolcock
authors.forename: Oleg
authors.initials: O
authors.lastname: Georgiev
authors.forename: Walter
authors.initials: W
authors.lastname: Schaffner
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D001483:Base Sequence; D002460:Cell Line; D053903:DNA Breaks, Double-Stranded; D004265:DNA Helicases / Q000235:genetics / Q000502:physiology*; D004260:DNA Repair; D029721:Drosophila Proteins / Q000235:genetics / Q000502:physiology*; D004331:Drosophila melanogaster / Q000201:enzymology / Q000235:genetics*; D049750:Genome, Insect; D008969:Molecular Sequence Data; D011995:Recombination, Genetic; D012091:Repetitive Sequences, Nucleic Acid; D017422:Sequence Analysis, DNA
chemical_list: D029721:Drosophila Proteins; D004265:DNA Helicases; C470639:blm protein, Drosophila