title: Drosophila rasiRNA pathway mutations disrupt embryonic axis specification through activation of an ATR/Chk2 DNA damage response.
abstract: Small repeat-associated siRNAs (rasiRNAs) mediate silencing of retrotransposons and the Stellate locus. Mutations in the Drosophila rasiRNA pathway genes armitage and aubergine disrupt embryonic axis specification, triggering defects in microtubule polarization as well as asymmetric localization of mRNA and protein determinants in the developing oocyte. Mutations in the ATR/Chk2 DNA damage signal transduction pathway dramatically suppress these axis specification defects, but do not restore retrotransposon or Stellate silencing. Furthermore, rasiRNA pathway mutations lead to germline-specific accumulation of gamma-H2Av foci characteristic of DNA damage. We conclude that rasiRNA-based gene silencing is not required for axis specification, and that the critical developmental function for this pathway is to suppress DNA damage signaling in the germline.
authors.affiliation: Program in Molecular Medicine and Program in Cell Dynamics, University of Massachusetts Medical School, Worcester, MA 01605, USA.
authors.forename: Carla
authors.initials: C
authors.lastname: Klattenhoff
authors.forename: Diana P
authors.initials: DP
authors.lastname: Bratu
authors.forename: Nadine
authors.initials: N
authors.lastname: McGinnis-Schultz
authors.forename: Birgit S
authors.initials: BS
authors.lastname: Koppetsch
authors.forename: Heather A
authors.initials: HA
authors.lastname: Cook
authors.forename: William E
authors.initials: WE
authors.lastname: Theurkauf
mesh_terms: D000818:Animals; D019521:Body Patterning / Q000235:genetics*; D018797:Cell Cycle Proteins / Q000378:metabolism*; D064447:Checkpoint Kinase 2; D053487:DEAD-box RNA Helicases / Q000378:metabolism; D004249:DNA Damage; D029721:Drosophila Proteins / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000166:cytology / Q000196:embryology* / Q000235:genetics* / Q000378:metabolism; D004625:Embryo, Nonmammalian / Q000166:cytology / Q000196:embryology / Q000378:metabolism; D005260:Female; D018095:Germ-Line Mutation; D008870:Microtubules / Q000378:metabolism; D008954:Models, Biological; D009154:Mutation / Q000235:genetics*; D010053:Ovary / Q000166:cytology / Q000473:pathology; D010448:Peptide Initiation Factors / Q000378:metabolism; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D021381:Protein Transport; D020365:RNA Helicases / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics*; D013489:Suppression, Genetic; D016211:Transforming Growth Factor alpha / Q000378:metabolism
chemical_list: D018797:Cell Cycle Proteins; D029721:Drosophila Proteins; D010448:Peptide Initiation Factors; D034741:RNA, Small Interfering; D016211:Transforming Growth Factor alpha; C436124:aub protein, Drosophila; C083730:grk protein, Drosophila; C091675:osk protein, Drosophila; D064447:Checkpoint Kinase 2; C444435:Mei-41 protein, Drosophila; D017346:Protein Serine-Threonine Kinases; C112435:lok protein, Drosophila; C484034:armi protein, Drosophila; C088269:vas protein, Drosophila; D053487:DEAD-box RNA Helicases; D020365:RNA Helicases