rasiRNAs, DNA damage, and embryonic axis specification
Graduate School of Biomedical Sciences; Program in Molecular Medicine and Program in Cell Dynamics
Life Sciences | Medicine and Health Sciences
Drosophila repeat-associated small interfering RNAs (rasiRNAs) have been implicated in retrotransposon and stellate locus silencing. However, mutations in the rasiRNA pathway genes armitage, spindle-E, and aubergine disrupt embryonic axis specification, triggering defects in microtubule organization and localization of osk and grk mRNAs during oogenesis. We show that mutations in mei-41 and mnk, which encode ATR and Chk2 kinases that function in DNA damage signal transduction, dramatically suppress the cytoskeletal and RNA localization defects associated with rasiRNA mutations. In contrast, stellate and retrotransposon silencing are not restored in mei-41 and mnk double mutants. We also find that armitage, aubergine, and spindle-E mutations lead to germ-line-specific accumulation of gamma-H2Av foci, which form at DNA double-strand breaks, and that mutations in armi lead to Chk2-dependent phosphorylation of Vasa, an RNA helicase required for axis specification. The Drosophila rasiRNA pathway thus appears to suppress DNA damage in the germ line, and mutations in this pathway block axis specification by activating an ATR/Chk2-dependent DNA damage response that disrupts microtubule polarization and RNA localization.
DOI of Published Version
Cold Spring Harb Symp Quant Biol. 2006;71:171-80. Link to article on publisher's site
Cold Spring Harbor symposia on quantitative biology
Theurkauf, William E.; Klattenhoff, Carla Andrea; Bratu, Diana P.; Schultz, Nadine; Koppetsch, Birgit S.; and Cook, Heather A., "rasiRNAs, DNA damage, and embryonic axis specification" (2007). GSBS Student Publications. 1247.