title: Altered dynein-dependent transport in piRNA pathway mutants.
abstract: Maintenance of genome integrity in germ cells is crucial for the success of future generations. In Drosophila, and mammals, transposable element activity in the germline can cause DNA breakage and sterility. Recent studies have shown that proteins involved in piRNA (PIWI-interacting RNA) biogenesis are necessary for retrotransposon silencing in the Drosophila germline. Females mutant for genes in the piRNA biogenesis pathway produce eggs with patterning defects that result from Chk-2 (checkpoint kinase-2) DNA damage checkpoint activation. Here we show that large ribonucleoprotein aggregates form in response to DNA damage checkpoint activation in egg chambers of females defective in piRNA biogenesis. Aggregate formation is specific to piRNA biogenesis mutants, as other mutations that activate the same Chk-2-dependent checkpoint do not cause aggregate formation. These aggregates contain components of the dynein motor machinery, retrotransposon RNA, and protein and axial patterning RNAs. Disruption of the aggregates by colcemid treatment leads to increased retrotransposon RNA levels, indicating that these structures may be the destination of retrotransposon RNA transport and may be degradation or sequestration sites. We propose that aggregate formation is a cellular response to protect germ cells from DNA damage caused by elevated retrotransposon expression.
authors.affiliation: Developmental Genetics Program, the Skirball Institute, New York University School of Medicine, 540 First Avenue, New York, NY 10016, USA.
authors.forename: Caryn
authors.initials: C
authors.lastname: Navarro
authors.forename: Simon
authors.initials: S
authors.lastname: Bullock
authors.forename: Ruth
authors.initials: R
authors.lastname: Lehmann
mesh_terms: D000818:Animals; D001483:Base Sequence; D001692:Biological Transport; D064447:Checkpoint Kinase 2; D004249:DNA Damage; D017931:DNA Primers; D004330:Drosophila; D029721:Drosophila Proteins / Q000235:genetics; D004398:Dyneins / Q000378:metabolism*; D005260:Female; D018398:Homeodomain Proteins / Q000235:genetics; D017403:In Situ Hybridization; D009154:Mutation; D017346:Protein Serine-Threonine Kinases / Q000235:genetics; D012313:RNA / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015534:Trans-Activators / Q000235:genetics; D016211:Transforming Growth Factor alpha / Q000235:genetics
chemical_list: D017931:DNA Primers; D029721:Drosophila Proteins; D018398:Homeodomain Proteins; D015534:Trans-Activators; D016211:Transforming Growth Factor alpha; C056478:bcd protein, Drosophila; C083730:grk protein, Drosophila; D012313:RNA; D064447:Checkpoint Kinase 2; D017346:Protein Serine-Threonine Kinases; C112435:lok protein, Drosophila; D004398:Dyneins